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Sample records for b-lymphocytes

  1. Spondylarthritis in the absence of B lymphocytes

    NARCIS (Netherlands)

    Baeten, Dominique; Kruithof, Elli; Breban, Maxime; Tak, Paul P.

    2008-01-01

    The highly effective treatment of rheumatoid arthritis by B cell depletion and the presence of B cells in the peripheral and axial lesions of patients with spondylarthritis (SpA) raise the question as to whether B lymphocytes could also be an appropriate therapeutic target in the latter disease. We

  2. [B lymphocyte stimulator in systemic lupus erythematosus].

    Science.gov (United States)

    Mercado, Ulises

    2012-01-01

    The B lymphocyte stimulator (BLyS) is an essential protein for the growth and survival of B cells. BLyS is expressed on monocytes, macrophages, and dendritic cells. BLyS binds to three receptors on B cells: BAFF-R, BCMA, and TACI. BLyS overexpression in mice leads to lupus-like syndrome, but not in all, whereas BLyS deficient mice results in a block of B cell development. High serum levels of BLyS can be detected in patients with lupus and rheumatoid arthritis. BLyS antagonists are an attractive target for treating autoimmune diseases.

  3. PDCA expression by B lymphocytes reveals important functional attributes.

    Science.gov (United States)

    Vinay, Dass S; Kim, Chang H; Chang, Kyung H; Kwon, Byoung S

    2010-01-15

    We have demonstrated in this study the existence of a PDCA-expressing functional B cell population (PDCA+ B lymphocytes), which differentiates from activated conventional B (PDCA-IgM+) lymphocytes. Stimulation with anti-micro, LPS, CpG oligodeoxynucleotide, HSV-1, or CTLA-4 Ig activates the PDCA+ B lymphocytes, leading to cell division and induction of type I IFNs and IDO. Notably, the PDCA+ B lymphocytes are capable of Ag-specific Ab production and Ig class switching, which is corroborated by transfer experiments in B- and PDCA+ B lymphocyte-deficient microMT mice. Importantly, in lupus-prone MRL-Fas(lpr) mice, PDCA+ B lymphocytes remain the principal source of autoantibodies. The PDCA+ B lymphocytes have phenotypes with plasmacytoid dendritic cells, but are a distinct cell population in that they develop from C-kit+B220+ pro-B precursors. Thus, our data suggest that not all PDCA+ cells are dendritic cell-derived plasmacytoid dendritic cells and that a significant majority is the PDCA+ B lymphocyte population having distinct phenotype and function.

  4. B-lymphocyte activation with an extract of Nocardia brasiliensis.

    Science.gov (United States)

    Ortiz-Oritz, L; Parks, D E; Lopez, J S; Weigle, W O

    1979-08-01

    An extract from the pathogenic actinomycete Nocardia brasiliensis was mitogenic for murine lymphocytes. This deoxyribonucleic acid-synthetic response of whole spleen cells peaked after 48 h in culture at concentrations of Nocardia extract ranging from 10 to 200 micrograms/ml. The extract appeared to be a mitogen for B lymphocytes since cultures of spleen cells from congenitally athymic nude (nu/nu) mice and of antithymocyte serum plus complement-treated spleen cells from conventional (+/+) mice responded as well as untreated spleen cells from normal +/+ mice. Furthermore, thymocytes did not respond mitogenically to the extract. Mitogenic responses were stimulated in spleen cells from H-2(a), H-2(b), H-2(d), and H-2(k) mice, including lipopolysaccharide-nonresponder C3H/HeJ mice. This Nocardia extract also stimulated polyclonal B-cell activation to the hapten trinitrophenyl, serum protein human gamma globulin, and several mammalian erythrocytes in cultures of cells from both euthymic and nude mice. Additionally, the requirement for helper T cells in the primary in vitro immune response to sheep erythrocytes could be circumvented by the addition of this Nocardia extract. These results indicate that an extract from the pathogen N. brasiliensis can nonspecifically activate murine B lymphocytes and raise the possibility that polyclonal activation of B lymphocytes may contribute to the pathogenesis of nocardiosis.

  5. Growing B Lymphocytes in a Three-Dimensional Culture System

    Science.gov (United States)

    Wu, J. H. David; Bottaro, Andrea

    2010-01-01

    A three-dimensional (3D) culture system for growing long-lived B lymphocytes has been invented. The capabilities afforded by the system can be expected to expand the range of options for immunological research and related activities, including testing of immunogenicity of vaccine candidates in vitro, generation of human monoclonal antibodies, and immunotherapy. Mature lymphocytes, which are the effectors of adaptive immune responses in vertebrates, are extremely susceptible to apoptotic death, and depend on continuous reception of survival-inducing stimulation (in the forms of cytokines, cell-to-cell contacts, and antigen receptor signaling) from the microenvironment. For this reason, efforts to develop systems for long-term culture of functional, non-transformed and non-activated mature lymphocytes have been unsuccessful until now. The bone-marrow microenvironment supports the growth and differentiation of many hematopoietic lineages, in addition to B-lymphocytes. Primary bone-marrow cell cultures designed to promote the development of specific cell types in vitro are highly desirable experimental systems, amenable to manipulation under controlled conditions. However, the dynamic and complex network of stromal cells and insoluble matrix proteins is disrupted in prior plate- and flask-based culture systems, wherein the microenvironments have a predominantly two-dimensional (2D) character. In 2D bone-marrow cultures, normal B-lymphoid cells become progressively skewed toward precursor B-cell populations that do not retain a normal immunophenotype, and such mature B-lymphocytes as those harvested from the spleen or lymph nodes do not survive beyond several days ex vivo in the absence of mitogenic stimulation. The present 3D culture system is a bioreactor that contains highly porous artificial scaffolding that supports the long-term culture of bone marrow, spleen, and lymph-node samples. In this system, unlike in 2D culture systems, B-cell subpopulations developing

  6. B lymphocytes not required for progression from insulitis to diabetes in non-obese diabetic mice.

    Science.gov (United States)

    Charlton, B; Zhang, M D; Slattery, R M

    2001-12-01

    Previous studies have implicated B lymphocytes in the pathogenesis of diabetes in the non-obese diabetic (NOD) mouse. While it is clear that B lymphocytes are necessary, it has not been clear at which stage of disease they play a role; early, late or both. To clarify when B lymphocytes are needed, T lymphocytes were transferred from 5-week-old NOD female mice to age-matched NOD/severe combined immunodeficiency (SCID) recipient mice. NOD/SCID mice, which lack functionally mature T and B lymphocytes, do not normally develop insulitis or insulin-dependent diabetes melitus (IDDM). The NOD/SCID mice that received purified T lymphocytes from 5-week-old NOD mice subsequently developed insulitis and diabetes even though they did not have detectable B lymphocytes. This suggests that while B lymphocytes may be essential for an initial priming event they are not requisite for disease progression in the NOD mouse.

  7. T-lymphocyte dependency of B-lymphocyte blastogenic response to phytomitogens

    International Nuclear Information System (INIS)

    Han, T.; Dadey, B.

    1978-01-01

    Human peripheral blood T and B lymphocytes were separated by a method based on the stable rosette formation of T lymphocytes with neuraminidase-treated sheep erythrocytes, followed by centrifugation over a Ficoll-Hypaque gradient. Monocytes were isolated from the T-depleted B lymphocyte preparation by allowing the monocytes to ingest iron particles and by subsequent centrifugation over a Ficoll-Hypaque gradient. The T lymphocytes responded extremely well to PHA and very well to PWM, while the B lymphocytes were unresponsive to either PHA or PWM. However, when the B lymphocytes were cultured together with irradiated autologous or allogeneic T lymphocytes (1 : 1,1:2 or 1 : 4 ratio), both PHA and PWM became mitogenic to B lymphocytes. Irradiated T lymphocytes alone did not respond to either PHA or PWM, indicating that the 3 H-thymidine incorporation seen in the mixed-cell culture was due to the activation of unirradiated B lymphocytes. The B lymphocytes failed to respond to these phytomitogens in the presence of lower concentrations of irradiated T lymphocytes. The monocytes were found to be incapable of helping the B lymphocytes to respond to PHA or PWM. (author)

  8. B lymphocyte depletion with the monoclonal antibody rituximab in Graves' disease: a controlled pilot study

    DEFF Research Database (Denmark)

    El Fassi, Daniel; Nielsen, Claus H; Bonnema, Steen Joop

    2007-01-01

    CONTEXT: Graves' disease (GD) is a common TSH receptor autoantibody (TRAb)-mediated disorder. Because B lymphocytes are important self-antigen presenting cells and precursors for antibody-secreting plasma cells, temporary B-lymphocyte depletion with the monoclonal antibody rituximab (RTX) might...

  9. Enriched environment and stress exposure influence splenic B lymphocyte composition.

    Science.gov (United States)

    Gurfein, Blake T; Hasdemir, Burcu; Milush, Jeffrey M; Touma, Chadi; Palme, Rupert; Nixon, Douglas F; Darcel, Nicholas; Hecht, Frederick M; Bhargava, Aditi

    2017-01-01

    Prolonged chronic stress has deleterious effects on immune function and is associated with numerous negative health outcomes. The spleen harbors one-fourth of the body's lymphocytes and mediates both innate and adaptive immune responses. However, the subset of splenic lymphocytes that respond, either adaptively or maladaptively, to various stressors remains largely unknown. Here we investigated the effects of unpredictable chronic mild stress (CMS) exposure on spleen composition in male mice housed in two different caging conditions: standard caging (Cntl) and enriched environment (EE). EE-caged mice exhibited the greatest absolute number of splenocytes and CMS exposure significantly lowered splenocyte numbers in both caging conditions. Glucocorticoid production, measured by mean fecal corticosterone metabolites (FCM), was significantly lower in EE-caged mice vs. Cntl-caged mice. Surprisingly, CMS exposure resulted in an increase in mean FCM in EE-caged mice, but no significant change in Cntl-caged mice. CMS altered the splenic B:T lymphocyte ratio; it reduced the frequency of B cells, but increased the frequency of T cells in EE-caged mice. Splenocyte number and B:T lymphocyte ratio showed a negative relationship with mean FCM. EE-caged mice had a lower frequency of immature and germinal B cells than Cntl-caged mice. CMS markedly increased the frequency of immature and marginal zone B cells, but decreased the frequency of follicular B cells in both caging conditions. Mean FCM correlated positively with frequency of immature, marginal zone and germinal center B cells, but negatively with frequency of follicular B cells. To conclude, splenic immune cells, particularly B lymphocyte composition, are modulated by caging environment and stress and may prime mice differently to respond to immune challenges.

  10. Lymphopenia and variations in T and B lymphocytes appearing immediately after irradiation

    International Nuclear Information System (INIS)

    Bolla, M.; Vrousos, C.; Bensa, J.C.; Kolodie, H.; Vincent, F.; Moulin, J.J.; Lachet, B.

    1979-01-01

    Immunity tests were conducted in 21 patients with cancer, before and two months after irradiation. T and B lymphocyte counts were normal before irradiation when compared to a control group. Lymphopenia was present after irradiation affecting mainly the T lymphocytes (P=0.005), whereas changes in B lymphocytes were not significant. These results suggest that irradiation has an immunosuppressive effect which should be studied in greater detail to establish possible therapeutic applications [fr

  11. B-lymphocytes as key players in chemical-induced asthma.

    Directory of Open Access Journals (Sweden)

    Vanessa De Vooght

    Full Text Available T-lymphocytes and B-lymphocytes are key players in allergic asthma, with B-lymphocytes producing antigen-specific immunoglobulins E (IgE. We used a mouse model of chemical-induced asthma and transferred B-lymphocytes from sensitized animals into naïve wild type mice, B-lymphocyte knock-out (B-KO mice or severe combined immunodeficiency (SCID mice. On days 1 and 8, BALB/c mice were dermally sensitized with 0.3% toluene diisocyanate (TDI (20 µl/ear. On day 15, mice were euthanized and the auricular lymph nodes isolated. B-lymphocytes (CD19(+ were separated from the whole cell suspension and 175,000 cells were injected in the tail vein of naïve wild type, B-KO or SCID mice. Three days later, the mice received a single oropharyngeal challenge with 0.01% TDI (20 µl or vehicle (acetone/olive oil (AOO (controls. Airway reactivity to methacholine and total and differential cell counts in the bronchoalveolar lavage (BAL fluid were measured 24 hours after challenge. B-lymphocytes of AOO or TDI-sensitized mice were characterized for the expression of surface markers and production of cytokines. We found that transfer of B-cells obtained from mice dermally sensitized to toluene diisocyanate (TDI into naïve wild type mice, B-KO mice or SCID mice led, within three days, to an acute asthma-like phenotype after an airway challenge with TDI. This response was specific and independent of IgE. These B-lymphocytes showed antigen presenting capacities (CD80/CD86 and CD40 and consisted of B effector (Be2- (IL-4 and Be1-lymphocytes (IFN-γ. The transferred B-lymphocytes were visualized near large airways, 24 hours after TDI challenge. Thus, B-lymphocytes can provoke an asthmatic response without the action of T-lymphocytes and without major involvement of IgE.

  12. B lymphocytes trigger monocyte mobilization and impair heart function after acute myocardial infarction

    Science.gov (United States)

    Zouggari, Yasmine; Ait-Oufella, Hafid; Bonnin, Philippe; Simon, Tabassome; Sage, Andrew P; Guérin, Coralie; Vilar, José; Caligiuri, Giuseppina; Tsiantoulas, Dimitrios; Laurans, Ludivine; Dumeau, Edouard; Kotti, Salma; Bruneval, Patrick; Charo, Israel F; Binder, Christoph J; Danchin, Nicolas; Tedgui, Alain; Tedder, Thomas F; Silvestre, Jean-Sébastien; Mallat, Ziad

    2014-01-01

    Acute myocardial infarction is a severe ischemic disease responsible for heart failure and sudden death. Here, we show that after acute myocardial infarction in mice, mature B lymphocytes selectively produce Ccl7 and induce Ly6Chi monocyte mobilization and recruitment to the heart, leading to enhanced tissue injury and deterioration of myocardial function. Genetic (Baff receptor deficiency) or antibody-mediated (CD20- or Baff-specific antibody) depletion of mature B lymphocytes impeded Ccl7 production and monocyte mobilization, limited myocardial injury and improved heart function. These effects were recapitulated in mice with B cell–selective Ccl7 deficiency. We also show that high circulating concentrations of CCL7 and BAFF in patients with acute myocardial infarction predict increased risk of death or recurrent myocardial infarction. This work identifies a crucial interaction between mature B lymphocytes and monocytes after acute myocardial ischemia and identifies new therapeutic targets for acute myocardial infarction. PMID:24037091

  13. Evidence for the replication of bovine leukemia virus in the B lymphocytes

    International Nuclear Information System (INIS)

    Paul, P.S.; Pomeroy, K.A.; Johnson, D.W.; Muscoplat, C.C.; Handwerger, B.S.; Soper, F.F.; Sorensen, D.K.

    1977-01-01

    Bovine peripheral blood lymphocytes from a cow with persistent lymphocytosis were separated on nylon wool columns into nylon-adherent and nonadherent populations. Nylon-adherent cells were highly enriched for surface immunoglobulin (SIg) bearing B lymphocytes (95.5%) and nonadherent cells for SIg negative non-B cells, presumably T lymphocytes (96.3%). The B lymphocytes were found to be the major producers for bovine leukemia virus. A total of 39% of the B-enriched cells, surviving after 72 hours in culture, produced bovine leukemia virus as compared with 0.5% of the non-B cells

  14. SPONTANEOUS IMMUNOGLOBULIN-SYNTHESIZING ACTIVITY OF B LYMPHOCYTES IN INFLAMMATORY RHEUMATIC DISEASES

    Directory of Open Access Journals (Sweden)

    A.T. T. Mamasaidov

    2007-01-01

    Full Text Available Abstract. The aim of present work was to evaluate clinical significance of B-lymphocytes spontaneous antibody-synthesizing activity by B-lymphocytes (LASA in patients with rheumatic inflammatory diseases (RD, i.e., reactive arthritis (ReA, ankylosing spondylitis (AS, rheumatoid arthritis (RA, and systemic lupus erythematosus (SLE. Significantly higher LASA levels were revealed in the patients with ReA, AS, RA, and SLE, as compared with healthy persons and patients with osteoarthrosis. Clinical significance of LASA indexes and their changes may reflect manifestation and degree of immunological activities in ReA, AS, RA, and SLE.

  15. Specific B lymphocyte suppression by infectious bursal agent (Gumboro disease virus) in chickens.

    Science.gov (United States)

    Hudson, L; Pattison, M; Thantrey, N

    1975-10-01

    Chickens infected experimentally with infectious bursal agent (IBA) during embryonation or early after hatching show a severe depression of bursa-dependent lymphoid components, and associated immune functions. Data presented here and elsewhere show that the degree of B cell suppression correlates with the time of infection. This would be compatible with a virus-induced block in B lymphocyte differentiation. Accordingly, the virus may be cytopathic for early (bursal) but not late (circulating) B lymphocytes or, more likely, the virus inactivates those non-lymphoid bursal cells mediating lymphocyte differentiation.

  16. Allogeneic hematopoietic stem cell transplantation as immunotherapy : B lymphocytes versus leukemia

    NARCIS (Netherlands)

    Gillissen, M.A.

    2018-01-01

    Research described in this thesis focuses on the role of B lymphocytes in graft versus leukemia responses following allogeneic hematopoietic stem cell transplantation (HSCT) as treatment of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Acute myeloid leukemia (AML) and high-risk

  17. Effects of aluminum on immune functions of cultured splenic T and B lymphocytes in rats.

    Science.gov (United States)

    She, Yue; Wang, Nan; Chen, Chongxiao; Zhu, Yanzhu; Xia, Shiliang; Hu, Chongwei; Li, Yanfei

    2012-06-01

    The effects of Aluminum (Al) exposure on immune functions of cultured splenic T and B lymphocytes of rats were studied. The lymphocytes were isolated from spleen of healthy male Wistar rats weighing 110-120 g. The cultured cells in RPMI-1640 medium were exposed to 0 (control group), 0.035 (low-dose group), 0.07 (medial-dose group), and 0.14 (high-dose group) mg/mL Al(3+) as aluminum trichloride (AlCl(3)) in an incubator under 5% CO(2) at 37°C for 24 h. The T and B lymphocyte proliferation was measured with a tetrazolium dye colorimetric assay. The levels of interleukin (IL)-2, IL-6, and tumor necrosis factor (TNF)-α were determined by iodine [(125)I] IL-2, IL-6, and TNF-α radioimmunoassay kits, respectively. The proportions of CD3(+), CD4(+), and CD8(+) T lymphocytes were measured with a flow cytometer. The results showed that the T and B lymphocyte proliferation, the levels of IL-2, IL-6, TNF-α, the proportions of CD3(+) and CD4(+) T lymphocytes, and the ratio of CD4(+)/CD8(+) T lymphocytes were lowered by Al treatments, while the proportion of CD8(+) T lymphocytes was increased. These findings indicate that Al exposure can inhibit the immune functions of splenic T and B lymphocytes of rats in vitro.

  18. Increased periodontal bone loss in temporarily B lymphocyte-deficient rats

    DEFF Research Database (Denmark)

    Klausen, B; Hougen, H P; Fiehn, N E

    1989-01-01

    In order to study the role of T lymphocytes and B lymphocytes in the development of marginal periodontitis, experiments were performed on specific-pathogen-free (SPF) rats with various immunologic profiles. The study comprised nude (congenitally T lymphocyte-deficient), thymus-grafted nude (T-lym...

  19. Stress, cortisol, and B lymphocytes: a novel approach to understanding academic stress and immune function.

    Science.gov (United States)

    McGregor, Bonnie A; Murphy, Karly M; Albano, Denise L; Ceballos, Rachel M

    2016-01-01

    Animal and human in vitro models suggest that stress-related B lymphocyte decrements are due to high levels of glucocorticoids which cause apoptosis of pre-B-cells as they emerge from the bone marrow. The present study sought to explore the relationships among distress, salivary cortisol, and human B lymphocytes in vivo. Distress (perceived stress, negative affect, depressive symptoms), lymphocyte phenotype, and salivary cortisol were assessed among first-year graduate students (n = 22) and a community control sample (n = 30) at the start of classes in the fall and the week immediately before spring preliminary exams. Compared to controls, students reported greater distress on all measures at each time point except baseline perceived stress. Hierarchical linear regression with necessary control variables was used to assess the effect of student status on the three measures of distress, the four measures of lymphocyte phenotype, and cortisol AUC and CAR over time (T1-T2). Student status was associated with a significant decrease in CD19 + B lymphocytes and flattened cortisol awakening response (CAR). Change in CAR was associated with the decrease in CD19 + B lymphocytes. Results indicated that there are significant associations among student status, flattening of CAR, and decrements in CD19 + lymphocytes.

  20. Epstein - Barr virus expression in Hodgkin's disease: Correlation withhistologic subtypes and T and B lymphocyte distribution

    International Nuclear Information System (INIS)

    Mourad, W.; Bazerbashi, S.; Alsohaibani, Mohamed O.; Saddik, M.

    1998-01-01

    The pathogenesis of Hodgkin's disease is linked to Epstein-Barr virus(EBV). Some histologic subtypes show a high level of viral expression. Theseinclude mixed cellularity (MCHD) and nodular sclerosis (NSHD) subtypes. GradeII NSHD is a more aggressive variant of HD. Lymphocyte predominant (LPHD) isa B cell lymphoproliferative disorder that has not been associated with EBVexpression. Infiltrating lymphocytes in HD are predominantly T lymphocytes,with minor component of B lymphocytes. In the current study, EBV expressionwas tested in cases of HD in relation to histologic subtypes. An attempt wasmade at correlating EBV expression with T and B lymphocyte distribution inlymph nodes involved by HD. Formalin-fixed paraffin-embedded tissue from 62cases of HD were tested for EBV and mRNA expression, using the EBER-1 probeand in situ hybridization. T and B lymphocyte distribution and their ratioswere evaluated using antibodies to T and B lymphocytes (UCHL-1 [CD45RO] andCD20, respectively), and the immunoperoxidase technique. The cases were seenin 38 male and 24 female patients, with an age range of 3 to 72 years (median25 years). There were 30 cases of grade I and 15 cases of grade II NSHD, 9cases of MCHD and 8 cases of LPHD. EBV mRNA expression was seen in 29 cases(46%). This expression was seen in 8 cases of grade I NSHD (26%), 13 cases ofgrade II NSHD (86%) and 8 cases of MCHD (88%). None of the cases of LPHDshowed viral expression. T to B lymphocytes ratios in EBV-positive casesranged from 1/6 to 8/1 and ranged from 2/1 to 20/1 in EBV-negative cases(P=0.06). Nine of the 29 positive cases (31%) showed equal T/B lymphocyteratios (n=4), or predominance of B lymphocytes (n=5). None of theEBV-negative cases showed predominance of B lymphocytes. Our study confirmedpreviously reported findings of the prevalence of EBV expression in MCHD andNSHD. Our findings also suggest that EBV expression may be more commonly seenin aggressive forms of HD. Decreased number of T lymphocytes in

  1. Variations of T and B lymphocytes of flounder (Paralichthys olivaceus) after Hirame novirhabdovirus infection and immunization.

    Science.gov (United States)

    Xing, Jing; Wang, Lei; Zhen, Mengxiao; Tang, Xiaoqian; Zhan, Wenbin

    2018-04-01

    T and B lymphocytes are closely related to immunization and pathogen infection. Our previous study confirmed the CD3 + , CD4-1 + , CD4-2 + , CD8β + T lymphocytes and IgM + B lymphocytes presented in the peripheral blood leukocytes (PBLs) of flounder (Paralichthys olivaceus), in this paper, the variations of T and B lymphocytes of flounder after Hirame novirhabdovirus (HIRRV) infection or immunization were investigated. The flounders were injected with live or inactivated HIRRV, then the percentages of T and B lymphocytes in PBLs were analyzed by Flow cytometry (FCM), total antibodies and HIRRV-specific antibodies in serum were detected by Enzyme-linked immunosorbent assay (ELISA), and expression of twelve immune-related genes in the head kidneys were determined using q-PCR. The results showed that the percentages of CD3 + , CD4-1 + , CD4-2 + , CD8β + T lymphocytes and IgM + B lymphocytes significantly increased in both infection and immunization groups, in infection group they decreased rapidly after the peak and significantly lower than control levels at the end of infection, in immunization group they went down steadily to the control levels at the end of immunization. The total antibodies and HIRRV-specific antibodies increased first and peaked on the 7 th day post infection and on the 14 th day post immunization, respectively, then gradually decreased to the control levels. Additionally, twelve immune-related genes were up-regulated in both groups. These results demonstrated that the HIRRV induced both humoral and cellular immunity of flounder, the lymphocytes varied more sharply in infection group than those in immunization group and CD8 + T lymphocytes responded much more than CD4 + T lymphocytes to HIRRV antigen. Copyright © 2018 Elsevier Ltd. All rights reserved.

  2. In vivo and in vitro modulation of HLA-DM and HLA-DO is induced by B lymphocyte activation

    NARCIS (Netherlands)

    Roucard, C.; Thomas, C.; Pasquier, M. A.; Trowsdale, J.; Sotto, J. J.; Neefjes, J.; van Ham, M.

    2001-01-01

    Ag presentation via HLA class II molecules in B lymphocytes depends on the coordinated action of HLA-DM, the catalyst of class II-peptide loading, and HLA-DO, a pH-dependent modulator of DM, the expression of which is almost completely restricted to B lymphocytes. The relative expression levels of

  3. Use of radiolabeled monoclonal anti-B1 antibody for B lymphocyte imaging in Rhesus monkeys

    International Nuclear Information System (INIS)

    Letvin, N.L.; Zalutsky, M.R.; Chalifoux, L.V.; Atkins, H.L.

    1987-01-01

    Imaging tissues rich in B lymphocytes in man using a radiolabeled monoclonal anti-B cell antibody would be extremely useful in the clinical staging of non-Hodgkins lymphomas. Studies were done in rhesus monkeys using radiolabeled monoclonal anti-B1 antibody to determine the feasibility of such an approach. Immunohistologic studies demonstrated that infused monoclonal anti-B1 binds in vivo with specificity to B cells in lymph nodes and spleen. The kinetics of clearance of 131 I-labeled anti-B1 were determined. The B lymphocyte-rich spleen could be readily visualized by gamma camera scanning without significant background and without the need for image intensification or blood background subtraction techniques. These data support the feasibility of using anti-B1 for staging B cell lymphomas in man. (author)

  4. mTOR-Dependent and Independent Survival Signaling by PI3K in B Lymphocytes

    OpenAIRE

    Kaileh, Mary; Vazquez, Estefania; MacFarlane, Alexander W.; Campbell, Kerry; Kurosaki, Tomohiro; Siebenlist, Ulrich; Sen, Ranjan

    2016-01-01

    Peripheral B lymphocyte survival requires the B cell receptor (BCR) and B cell activating factor (BAFF) binding to its receptor (BAFF-R). Deletion of the BCR, or its signal transducing chaperone Ig?, leads to rapid loss of mature B cells, indicating that signals initiated at the BCR are crucial for B cell survival. BAFF or BAFF-R deficiency also significantly reduces the numbers of mature B cells despite normal BCR expression. Together, these observations indicate that continued BCR and BAFF-...

  5. Comprehensive Proteomic Investigation of Ebf1 Heterozygosity in Pro-B Lymphocytes Utilizing Data Independent Acquisition.

    Science.gov (United States)

    Musa, Yaarub R; Boller, Sören; Puchalska, Monika; Grosschedl, Rudolf; Mittler, Gerhard

    2018-01-05

    Early B cell factor 1 (EBF1) is one of the key transcription factors required for orchestrating B-cell lineage development. Although studies have shown that Ebf1 haploinsufficiency is involved in the development of leukemia, no study has been conducted that characterizes the global effect of Ebf1 heterozygosity on the proteome of pro-B lymphocytes. Here, we employ both data independent acquisition (DIA) and shotgun data dependent acquisition (DDA) workflows for profiling proteins that are differently expressed between Ebf1 +/+ and Ebf1 +/- cells. Both DDA and DIA were able to reveal the downregulation of the EBF1 transcription factor in Ebf1 +/- pro-B lymphocytes. Further examination of differentially expressed proteins by DIA revealed that, similar to EBF1, the expression of other B-cell lineage regulators, such as TCF3 and Pax5, is also downregulated in Ebf1 heterozygous cells. Functional DIA analysis of differentially expressed proteins showed that EBF1 heterozygosity resulted in the deregulation of at least eight transcription factors involved in lymphopoiesis and the deregulation of key proteins playing crucial roles in survival, development, and differentiation of pro-B lymphocytes.

  6. Elevated D8/17 expression on B lymphocytes, a marker of rheumatic fever, measured with flow cytometry in tic disorder patients

    NARCIS (Netherlands)

    Hoekstra, PJ; Bijzet, J; Limburg, PC; Steenhuis, MP; Troost, PW; Oosterhoff, MD; Korf, J; Kallenberg, CGM; Minderaa, RB

    Objective: Elevated D8/17 expression on B lymphocytes is a known susceptibility marker of rheumatic fever. Previous studies have reported higher than usual D8/ 17 expression on B lymphocytes of patients with tic disorders. The purpose of this study was to assess D8/17 expression on B lymphocytes of

  7. [Modulating the survival and maturation system of B lymphocytes: Current and future new therapeutic strategies in systemic lupus erythematosus].

    Science.gov (United States)

    Valor, Lara; López-Longo, Francisco Javier

    2015-09-07

    Systemic lupus erythematosus is an autoimmune disease associated with an aberrant production of autoantibodies by self-reactive B lymphocytes. The study of the phenotypic characteristics of B lymphocytes and the identification of their surface receptors such as BAFF-R, TACI and BCMA, which are responsible of their survival and maturation, have contributed to the development of new therapeutic strategies in recent years. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  8. Interaction of Epstein-Barr virus (EBV) with human B-lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    Klein, George, E-mail: Georg.Klein@ki.se [Karolinska Institutet, Department of Microbiology, Tumor and Cell Biology (MTC), Box 280, S171 77 Stockholm (Sweden); Klein, Eva; Kashuba, Elena [Karolinska Institutet, Department of Microbiology, Tumor and Cell Biology (MTC), Box 280, S171 77 Stockholm (Sweden)

    2010-05-21

    Epstein-Barr virus, EBV, and humans have a common history that reaches back to our primate ancestors. The virus co-evolved with man and has established a largely harmless and highly complex co-existence. It is carried as silent infection by almost all human adults. A serendipitous discovery established that it is the causative agent of infectious mononucleosis. Still, EBV became known first in 1964, in a rare, geographically prevalent malignant lymphoma of B-cell origin, Burkitt lymphoma BL. Its association with a malignancy prompted intensive studies and its capacity to immortalize B-lymphocytes in vitro was soon demonstrated. Consequently EBV was classified therefore as a potentially tumorigenic virus. Despite of this property however, the virus carrier state itself does not lead to malignancies because the transformed cells are recognized by the immune response. Consequently the EBV induced proliferation of EBV carrying B-lymphocytes is manifested only under immunosuppressive conditions. The expression of EBV encoded genes is regulated by the cell phenotype. The virus genome can be found in malignancies originating from cell types other than the B-lymphocyte. Even in the EBV infected B-cell, the direct transforming capacity is restricted to a defined window of differentiation. A complex interaction between virally encoded proteins and B-cell specific cellular proteins constitute the proliferation inducing program. In this short review we touch upon aspects which are the subject of our present work. We describe the mechanisms of some of the functional interactions between EBV encoded and cellular proteins that determine the phenotype of latently infected B-cells. The growth promoting EBV encoded genes are not expressed in the virus carrying BL cells. Still, EBV seems to contribute to the etiology of this tumor by modifying events that influence cell survival and proliferation. We describe a possible growth promoting mechanism in the genesis of Burkitt lymphoma

  9. Application of a new ultra-microculture system. II. Stimulation of human B lymphocytes.

    Science.gov (United States)

    Ulmer, A J; Gruber, M; Flad, H D

    1988-07-22

    An ultra-microtechnique for culturing human B-lymphocytes in glass capillary tubes using a volume of 2 microliter is described. The advantage of this ultra-microculture system is that only a small number of lymphocytes and minute amounts of culture medium (or test factors) are required. Optimal culture conditions for the formation of Ig-secreting plaque-forming cells (PFC) after stimulation of mononuclear cells with pokeweed mitogen are given. Furthermore it is shown that immunoglobulin secreted into culture supernatants by purified B cells in the presence of T cell subsets can be measured in a microELISA.

  10. B Lymphocyte Lineage Specification, Commitment and Epigenetic Control of Transcription by Early B Cell Factor 1

    OpenAIRE

    Hagman, James; Ramírez, Julita; Lukin, Kara

    2012-01-01

    Early B cell factor 1 (EBF1) is a transcription factor that is critical for both B lymphopoiesis and B cell function. EBF1 is a requisite component of the B lymphocyte transcriptional network and is essential for B lineage specification. Recent studies revealed roles for EBF1 in B cell commitment. EBF1 binds its target genes via a DNA-binding domain including a unique ‘zinc knuckle’, which mediates a novel mode of DNA recognition. Chromatin immunoprecipitation of EBF1 in pro-B cells defined h...

  11. Lymph node B lymphocyte trafficking is constrained by anatomy and highly dependent upon chemoattractant desensitization

    Science.gov (United States)

    Park, Chung; Hwang, Il-Young; Sinha, Rajesh K.; Kamenyeva, Olena; Davis, Michael D.

    2012-01-01

    B lymphocyte recirculation through lymph nodes (LNs) requires crossing endothelial barriers and chemoattractant-triggered cell migration. Here we show how LN anatomy and chemoattractant receptor signaling organize B lymphocyte LN trafficking. Blood-borne B cells predominately used CCR7 signaling to adhere to high endothelial venules (HEVs). New B cell emigrants slowly transited the HEV perivenule space, and thereafter localized nearby, avoiding the follicle. Eventually, the newly arrived B cells entered the basal portion of the follicle gradually populating it. In contrast, newly arriving activated B cells rapidly crossed HEVs and migrated toward the lymph node follicle. During their LN residency, recirculating B cells reacquired their sphingosine-1 phospate receptor 1 (S1P1) receptors and markedly attenuated their sensitivity to chemokines. Eventually, the B cells exited the LN follicle by entering the cortical lymphatics or returning to the paracortical cords. Upon entering the lymph, the B cells lost their polarity, down-regulated their S1P1 receptors, and subsequently strongly up-regulated their sensitivity to chemokines. These results are summarized in a model of homeostatic trafficking of B cells through LNs. PMID:22039261

  12. The effect of deoxyguanosine on human lymphocyte function. II. Analysis of the interference with B lymphocyte differentiation in vitro.

    Science.gov (United States)

    Spaapen, L J; Rijkers, G T; Staal, G E; Rijksen, G; Duran, M; Stoop, J W; Zegers, B J

    1984-05-01

    The differentiation of normal human peripheral blood B lymphocytes into plasma cells in vitro, studied in mononuclear cells stimulated with PWM or in purified B cells stimulated with a T cell-replacing factor (TRF), can be inhibited by both deoxyguanosine (dGuo) and guanosine. The mechanism underlying this effect, which differs from the in vivo findings in PNP deficiency, was analyzed. dGuo toxicity can be antagonized by hypoxanthine but not by deoxycytidine. PNP-deficient and HGPRT-deficient B lymphocytes are not sensitive to the intoxicating properties of (deoxy)guanosine. Inhibition of PNP activity in normal B lymphocytes by 8-aminoguanosine decreases the sensitivity for dGuo intoxication. Incubation of purified B cells (stimulated with TRF) with dGuo leads to increased intracellular levels of guanosine di- and triphosphate (GDP and GTP), whereas deoxyguanosine triphosphate (dGTP) levels remain low. These observations lead to the conclusion that inhibition of B lymphocyte differentiation by dGuo is brought about by one of the end products of the pathway starting with degradation of dGuo by PNP, followed by guanine salvage by HGPRT, and possibly further phosphorylation of GMP into GDP and GTP. According to this mechanism, B lymphocyte differentiation in PNP deficiency is not sensitive to (deoxy)guanosine; because of the absence of PNP activity, these cells cannot accumulate GMP, GDP, and GTP, and therefore escape dGuo intoxication.

  13. PHENOTYPIC PROFILE OF B-LYMPHOCYTES IN WOMEN WITH CHRONIC ENDOMETRITIS AND ADNEXITIS

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    A. A. Savchenko

    2016-01-01

    Full Text Available The aim of this study was to investigate phenotypic profile of B lymphocytes in peripheral blood of the patients with chronic endometritis and adnexitis. The study involved 89 women in their reproductive age (18 to 45 years with chronic endometritis (48 cases and adnexitis (41 cases. Ninety-eight healthy agematched women participated as a control group. Phenotypic B-cell subpopulations were analyzed by flow cytometry performed with direct immunofluorescent staining of peripheral cells from whole blood using the following antibody panel: CD5-FITC/CD23-PE/CD19-ECD/CD45-PC5/CD27-PC7. A significantly reduced B-lymphocyte content was revealed in peripheral blood of women with chronic endometritis and adnexitis. The reduced cell numbers occurred due to reduced B2 (main fraction of B-lymphocytes and as B1 cells (minor fraction which determines insufficient reactivity of specific humoral immune response, including immune reactions at the mucous membranes. However, percentage of B2-lymphocytes was decreased only in endometriosis, whereas patients with adnexitis showed decrease in both relative and absolute counts of this B cell subpopulation. A decreased content of naive B-cells in the peripheral blood is another feature of the B cell phenotypic profile in chronic endometritis and adnexitis. Moreover, the drop of the naive B-cell levels in patients with adnexitis proved to be more pronounced than in persons with endometritis. Expression of CD23- antigen (a low-affinity receptor for IgE has been investigated as a functional marker of B cells. All the studied peripheral B cell subpopulations expressing CD23 were decreased in the patients with chronic endometritis. The numbers of different B cell fractions expressing CD23 antigen were also reduced in the women with chronic adnexitis as compared to the levels detected in patients with chronic endometritis. Alterations of the B-cell immunity were more pronounced in chronic adnexitis, due to more extensive

  14. B-lymphocyte subpopulations in patients with selective IgA deficiency.

    Science.gov (United States)

    Nechvatalova, Jana; Pikulova, Zdenka; Stikarovska, Dagmar; Pesak, Sava; Vlkova, Marcela; Litzman, Jiri

    2012-06-01

    Selective deficiency IgA (IgAD) is the most common primary abnormality of immunoglobulin production with unknown pathophysiology. It is genetically related to common variable immunodeficiency (CVID), where besides IgA also IgG and frequently IgM serum levels are decreased. In this study we focused on determination of B-lymphocyte developmental stages and searching for similarities between CVID and IgAD. Using flow cytometry we determined major lymphocyte subpopulations and B-lymphocyte subsets: naïve (CD27(-)IgD(+)), marginal zone cells (CD27(+)IgD(+)), class-switched memory cells (CD27(+)IgD(-)), "double-negative" B cells (CD27(-)IgD(-)), transitional cells (IgM(++)CD38(++)), plasmablasts (CD38(+++)IgM(+) or IgM(-)), and CD21(low)CD38(low) cells in 80 patients with IgAD, 48 patients with CVID, and 80 control persons. Compared to healthy controls, a decrease in the absolute number and frequency of CD4+ cells (both < 0.001) was observed in IgAD patients. A decrease in the frequency of switched memory cells (P < 0.001), transitional cells (P = 0.035) as well as plasmablasts (P < 0.001) and an increase in the CD21(low)CD38(low) subset (P = 0.007) was observed in IgAD patients compared to control persons. No significant differences were observed in the remaining B-cell developmental subsets. A decrease in CD27(+)IgD(-) (<0.4% of peripheral blood lymphocytes), frequently observed in CVID patients and also previously reported in IgAD, was found in only five patients (6%) with IgAD, two of them being first-degree relatives of CVID patients. Our results show a decrease of terminally differentiated B-lymphocyte subsets in patients with IgAD, similar as previously found in patients with CVID, but these results are less expressed than in CVID patients.

  15. [Assesment of the selected T and B lymphocyte subsets in children with newly diagnosed insulin-dependent diabetes mellitus].

    Science.gov (United States)

    Kowalska, H; Kadziela, K; Wasik, M; Kowalska, M; Rybczyńska, J; Rymkiewicz-Kluczyńska, B

    2001-01-01

    The study was performed in 39 children with newly diagnosed insulin-dependent diabetes mellitus. The %age number of CD19+, CD5+/CD20+ B lymphocytes and CD3+, CD4+, CD8+, CD4+/DR+, CD8+/DR+ T lymphocytes subpopulations were investigated in the peripheral blood. Marked, statistically significant increase (p<0.0001) in CD5+ B lymphocytes was revealed in 77% of patients as compared to the healthy control. The elevated number of CD5+ B lymphocytes correlated with presence of activated lymphocytes T (CD4+/DR+ and CD8+/DR+). The total number of CD19+, CCD3+, CD4+, CD8+ lymphocytes was on comparable level in both groups.

  16. B lymphocyte lineage specification, commitment and epigenetic control of transcription by early B cell factor 1.

    Science.gov (United States)

    Hagman, James; Ramírez, Julita; Lukin, Kara

    2012-01-01

    Early B cell factor 1 (EBF1) is a transcription factor that is critical for both B lymphopoiesis and B cell function. EBF1 is a requisite component of the B lymphocyte transcriptional network and is essential for B lineage specification. Recent studies revealed roles for EBF1 in B cell commitment. EBF1 binds its target genes via a DNA-binding domain including a unique 'zinc knuckle', which mediates a novel mode of DNA recognition. Chromatin immunoprecipitation of EBF1 in pro-B cells defined hundreds of new, as well as previously identified, target genes. Notably, expression of the pre-B cell receptor (pre-BCR), BCR and PI3K/Akt/mTOR signaling pathways is controlled by EBF1. In this review, we highlight these current developments and explore how EBF1 functions as a tissue-specific regulator of chromatin structure at B cell-specific genes.

  17. Increased periodontal bone loss in temporarily B lymphocyte-deficient rats

    DEFF Research Database (Denmark)

    Klausen, B; Hougen, H P; Fiehn, N E

    1989-01-01

    In order to study the role of T lymphocytes and B lymphocytes in the development of marginal periodontitis, experiments were performed on specific-pathogen-free (SPF) rats with various immunologic profiles. The study comprised nude (congenitally T lymphocyte-deficient), thymus-grafted nude (T...... readily, but the spirochete strain could not be established permanently in the oral cavity of the rats, 95% of the inoculated rats raised serum IgG or IgM antibody against one or more of the microorganisms; nude rats tended to raise less antibody than the three other experimental groups. Inoculated rats...... had significantly less periodontal bone support than controls. Anti-mu treated inoculated rats had significantly less periodontal bone support than nude and normal rats, whereas no difference was found between normal, nude, and thymus-grafted rats. It is concluded that permanent T...

  18. Intravital two-photon imaging of adoptively transferred B lymphocytes in inguinal lymph nodes.

    Science.gov (United States)

    Park, Chung; Hwang, Il-Young; Kehrl, John H

    2009-01-01

    Intravital two-photon imaging allows the observation of immune cells in intact organs of live animals in real time. Recently, several studies using two-photon microscopy have detailed the motility of mouse B and T lymphocyte within lymph nodes and have shown a dependence upon chemokine receptor signaling for the basal velocity of the cells. For, example, T cells from Gnia2 (-/-)mice, deficient in the heterotrimer G-protein G alpha subunit G(alpha i2) have markedly impaired chemokine-triggered chemotaxis. In vivo these cells have reduced motility and impaired positioning within lymph nodes. Gnia2 (-/-) B cells exhibit similar defects. In addition, B cells from Rgs1 (-/-) mice, deficient in a major negative regulator of G(alpha i), have a more robust motility than do wild-type B cells. Here, we describe procedures for visualizing the behavior of fluorescently labeled and adoptively transferred B lymphocytes within the inguinal lymph node of live mice.

  19. Large-scale in vitro expansion of polyclonal human switched-memory B lymphocytes.

    Directory of Open Access Journals (Sweden)

    Sonia Néron

    Full Text Available Polyclonal preparations of therapeutic immunoglobulins, namely intravenous immunoglobulins (IVIg, are essential in the treatment of immunodeficiency and are increasingly used for the treatment of autoimmune and inflammatory diseases. Currently, patients' accessibility to IVIg depends exclusively upon volunteer blood donations followed by the fractionation of pooled human plasma obtained from thousands of individuals. Presently, there are no in vitro cell culture procedures allowing the preparation of polyclonal human antibodies. All in vitro human therapeutic antibodies that are currently generated are based on monoclonal antibodies, which are mostly issued from genetic engineering or single cell antibody technologies. Here, we describe an in vitro cell culture system, using CD40-CD154 interactions, that leads to a 1×10(6-fold expansion of switched memory B lymphocytes in approximately 50 days. These expanded cells secrete polyclonal IgG, which distribution into IgG(1, IgG(2, IgG(3 and IgG(4 is similar to that of normal human serum. Such in vitro generated IgG showed relatively low self-reactivity since they interacted moderately with only 24 human antigens among a total of 9484 targets. Furthermore, up to one liter of IgG secreting cells can be produced in about 40 days. This experimental model, providing large-scale expansion of human B lymphocytes, represents a critical step toward the in vitro production of polyclonal human IgG and a new method for the ex vivo expansion of B cells for therapeutic purposes.

  20. Trans-chromosomal recombination within the Ig heavy chain switch region in B lymphocytes

    Science.gov (United States)

    Kingzette, Mae; Spieker-Polet, Helga; Yam, Pi-Chen; Zhai, Shi-Kang; Knight, Katherine L.

    1998-01-01

    Somatic DNA rearrangements in B lymphocytes, including V(D)J gene rearrangements and isotype switching, generally occur in cis, i. e., intrachromosomally. We showed previously, however, that 3 to 7% of IgA heavy chains have the VH and Cα regions encoded in trans. To determine whether the trans-association of VH and Cα occurred by trans-chromosomal recombination, by trans-splicing, or by trans-chromosomal gene conversion, we generated and analyzed eight IgA-secreting rabbit hybridomas with trans-associated VH and Cα heavy chains. By ELISA and by nucleotide sequence analysis we found that the VH and Cα regions were encoded by genes that were in trans in the germline. We cloned the rearranged VDJ-Cα gene from a fosmid library of one hybridoma and found that the expressed VH and Cα genes were juxtaposed. Moreover, the juxtaposed VH and Cα genes originated from different IgH alleles. From the same hybridoma, we also identified a fosmid clone with the other expected product of a trans-chromosomal recombination. The recombination breakpoint occurred within the Sμ/Sα region, indicating that the trans-association of VH and Cα genes occurred by trans-chromosomal recombination during isotype switching. We conclude that trans-chromosomal recombination occurs at an unexpectedly high frequency (7%) within the IgH locus of B lymphocytes in normal animals, which may explain the high incidence of B-cell tumors that arise from oncogene translocation into the IgH locus. PMID:9751752

  1. Tumor-infiltrating B lymphocytes as an efficient source of highly specific immunoglobulins recognizing tumor cells

    Directory of Open Access Journals (Sweden)

    Pelliccia Angela

    2007-10-01

    Full Text Available Abstract Background There is much evidence that tumor cells elicit a humoral immune response in patients. In most cases, the presence of antibodies in peripheral blood is detected only in small proportion of patients with tumors overexpressing the corresponding antigen. In the present study, we analyzed the significance of local humoral response provided by tumor-infiltrating lymphocytes in breast cancer patients. Methods The ability of a patient's immune system to produce specific antibodies inside tumor tissue, capable of recognizing tumor cells, was explored through analysis of the oligoclonality of antibodies derived from tumor-infiltrating lymphocytes and construction of a series of recombinant antibody libraries in scFv format, derived from breast tumor-infiltrating B lymphocytes. These libraries and one from peripheral blood lymphocytes of a single breast cancer patient were panned against three purified surface tumor antigens, such as CEA, MUC1 and ED-B domain, and against intact MCF7 breast carcinoma cells. Results Application of novel display vector, pKM19, allowed isolation of a large panel of breast cancer-specific antibodies against known tumor antigens, as well as against breast carcinoma cells. Reactivity of novel scFvs was confirmed by ELISA, immunohistochemistry, fluorescence staining and flow cytometry. We demonstrated that seven of ten primary breast tumor specimens, obtained using discarded surgical material, could be exploited as an appropriate source for generation of phage display libraries, giving highly specific antitumor antibodies which recognize heterologous tumor cells. Conclusion Local humoral immune response within tumor tissue in breast cancer patients frequently has an oligoclonal character. Efficient selection of specific antitumor antibodies from recombinant antibody libraries, derived from such oligoclonal tumor-infiltrated B lymphocytes, indicates the presence of natural immune response against tumor antigens

  2. Selective toxicity of persian gulf sea cucumber holothuria parva on human chronic lymphocytic leukemia b lymphocytes by direct mitochondrial targeting.

    Science.gov (United States)

    Salimi, Ahmad; Motallebi, Abbasali; Ayatollahi, Maryam; Seydi, Enayatollah; Mohseni, Ali Reza; Nazemi, Melika; Pourahmad, Jalal

    2017-04-01

    Natural products isolated from marine environment are well known for their pharmacodynamic potential in diversity of disease treatments such as cancer or inflammatory conditions. Sea cucumbers are one of the marine animals of the phylum Echinoderm. Many studies have shown that the sea cucumber contains antioxidants and anti-cancer compounds. Chronic lymphocytic leukemia (CLL) is a disease characterized by the relentless accumulation of CD5 + B lymphocytes. CLL is the most common leukemia in adults, about 25-30% of all leukemias. In this study B lymphocytes and their mitochondria (cancerous and non-cancerous) were obtained from peripheral blood of human subjects and B lymphocyte cytotoxicity assay, and caspase 3 activation along with mitochondrial upstream events of apoptosis signaling including reactive oxygen species (ROS) production, collapse of mitochondrial membrane potential (MMP) and mitochondrial swelling were determined following the addition of Holothuria parva extract to both cancerous and non-cancerous B lymphocytes and their mitochondria. Our in vitro finding showed that mitochondrial ROS formation, MMP collapse, and mitochondrial swelling and cytochrome c release were significantly (P < 0.05) increased after addition of different concentrations of H. parva only in cancerous BUT NOT normal non-cancerous mitochondria. Consistently, different concentrations of H. parva significantly (P < 0.05) increased cytotoxicity and caspase 3 activation only in cancerous BUT NOT normal non-cancerous B lymphocytes. These results showed that H. parva methanolic extract has a selective mitochondria mediated apoptotic effect on chronic lymphocytic leukemia B lymphocytes hence may be promising in the future anticancer drug development for treatment of CLL. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1158-1169, 2017. © 2016 Wiley Periodicals, Inc.

  3. Segregation of B lymphocytes into stationary apoptotic and migratory proliferating subpopulations in agglomerate cultures with ileal epithelium.

    Science.gov (United States)

    Alitheen, N; McClure, S; McCullagh, P

    2001-09-01

    The B lymphocyte-epithelial cell interactions that define the microenvironment of the ileal Peyer's patch, the primary B lymphocyte organ of the fetal lamb, have been replicated in tissue culture. Mixed suspensions of ileal epithelial cells, lymphocytes and fibroblasts from fetuses of 63-103 days of gestation organized into macroscopically visible agglomerates within 72 h. These agglomerates contained translucent spherical cavities and were enclosed within a marginal cell layer and surrounded by an expanding corona of emigrating cells. The lining of the cavities and the marginal layer consisted of well-differentiated, polarized columnar ileal epithelial cells. One population of B lymphocytes in the initial mixed suspension differentiated into two discrete populations reproducing the characteristics of intact fetal ileal Peyer's patches. B cells apposed to follicle-associated epithelium (FAE) within agglomerates underwent apoptosis. The other population of emigrant B cells proliferated and expressed the BAQ44A differentiation marker. Differentiation of ileal epithelial cells into FAE, typical of Peyer's patches, was markedly accelerated. The mutually inductive influences of intestinal epithelial cells and B lymphocytes in these agglomerates replicate normal mid-gestational fetal development of the mucosal immune system and afford new opportunities for its further investigation.

  4. mTOR-Dependent and Independent Survival Signaling by PI3K in B Lymphocytes.

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    Mary Kaileh

    Full Text Available Peripheral B lymphocyte survival requires the B cell receptor (BCR and B cell activating factor (BAFF binding to its receptor (BAFF-R. Deletion of the BCR, or its signal transducing chaperone Igβ, leads to rapid loss of mature B cells, indicating that signals initiated at the BCR are crucial for B cell survival. BAFF or BAFF-R deficiency also significantly reduces the numbers of mature B cells despite normal BCR expression. Together, these observations indicate that continued BCR and BAFF-R signaling are essential for the survival of mature resting B cells in the periphery. Here we demonstrate that tonic BCR signals up-regulate p100 (Nfkb2 as well as Mcl-1 protein expression at a post-transcriptional level via a PI3K-dependent pathway. p100 expression is mTOR-independent, whereas Mcl-1 expression is mTOR-dependent. BAFF treatment further elevated Mcl-1 levels by an mTOR-independent pathway, while consuming p100. Accordingly, Mcl-1 induction by BAFF is abrogated in Nfkb2-/- B cells. We propose that the cumulative effects of the BCR and BAFF-R signaling pathways increase Mcl-1 levels beyond the threshold required for B cell survival.

  5. Chicoric acid suppresses BAFF expression in B lymphocytes by inhibiting NF-κB activity.

    Science.gov (United States)

    Chen, Lingxi; Huang, Gang; Gao, Min; Shen, Xiaodong; Gong, Wei; Xu, Zhizhen; Zeng, Yijun; He, Fengtian

    2017-03-01

    B cell activating factor belonging to the TNF family (BAFF) plays a critical role in the pathogenesis of autoimmune diseases. The inhibition of BAFF expression is an emerging therapeutic approach for these disorders. Chicoric acid (CA), a bioactive phytochemical found in several widely used traditional medicinal plants, has significant anti-inflammatory activity and anti-arthritic effects. However, the role of CA in modulation of BAFF expression remains unknown. In this study, we demonstrated that CA reduced BAFF expression in human B lymphocyte cell lines and decreased the DNA-binding activity of nuclear factor-κB (NF-κB) in the BAFF promoter region. Furthermore, CA inhibited both the nuclear translocation of p65 (the subunit of NF-κB) and the phosphorylation of IκBα (inhibitor of NF-κB). These results suggest that CA suppresses BAFF expression by inhibiting NF-κB activity, and CA may serve as a novel therapeutic agent to down-regulate excessive BAFF expression in autoimmune diseases. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. mTOR-Dependent and Independent Survival Signaling by PI3K in B Lymphocytes.

    Science.gov (United States)

    Kaileh, Mary; Vazquez, Estefania; MacFarlane, Alexander W; Campbell, Kerry; Kurosaki, Tomohiro; Siebenlist, Ulrich; Sen, Ranjan

    2016-01-01

    Peripheral B lymphocyte survival requires the B cell receptor (BCR) and B cell activating factor (BAFF) binding to its receptor (BAFF-R). Deletion of the BCR, or its signal transducing chaperone Igβ, leads to rapid loss of mature B cells, indicating that signals initiated at the BCR are crucial for B cell survival. BAFF or BAFF-R deficiency also significantly reduces the numbers of mature B cells despite normal BCR expression. Together, these observations indicate that continued BCR and BAFF-R signaling are essential for the survival of mature resting B cells in the periphery. Here we demonstrate that tonic BCR signals up-regulate p100 (Nfkb2) as well as Mcl-1 protein expression at a post-transcriptional level via a PI3K-dependent pathway. p100 expression is mTOR-independent, whereas Mcl-1 expression is mTOR-dependent. BAFF treatment further elevated Mcl-1 levels by an mTOR-independent pathway, while consuming p100. Accordingly, Mcl-1 induction by BAFF is abrogated in Nfkb2-/- B cells. We propose that the cumulative effects of the BCR and BAFF-R signaling pathways increase Mcl-1 levels beyond the threshold required for B cell survival.

  7. High expression of 5-lipoxygenase in normal and malignant mantle zone B lymphocytes

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    Sander Birgitta

    2009-01-01

    Full Text Available Abstract Background Human B lymphocytes can produce leukotriene B4 but the biological function of the 5-lipoxygenase (5-LO pathway in B cells is unclear. In order to better understand and define the role of 5-LO in B cells, we investigated the expression of 5-LO mRNA and protein in subsets of B cells from human tonsils and different types of B cell lymphoma. Results Based on RT-PCR and western blot/immunohistochemical staining, with a polyclonal antibody raised against 5-LO, high expression of 5-LO was found in mantle zone B cells from tonsils. By contrast, only a weak expression of 5-LO was detected in germinal centre cells and no expression in plasma cells from tonsils. This pattern of 5-LO expression was preserved in malignant lymphoma with high expression in mantle B cell lymphoma (MCL and weak or no expression in follicular lymphoma. Primary leukemized MCL, so called B-prolymphocytic leukaemia cells, and MCL cell lines also expressed 5-LO and readily produced LTB4 after activation. Conclusion The present report demonstrates the expression of 5-LO mainly in normal and malignant mantle zone B cells while the expression is low or absent in germinal centre B cells and plasma cells, indicating a role of the 5-LO pathway in B cells before the cells finally differentiate to plasma cells.

  8. Runx1-Cbfβ facilitates early B lymphocyte development by regulating expression of Ebf1.

    Science.gov (United States)

    Seo, Wooseok; Ikawa, Tomokatsu; Kawamoto, Hiroshi; Taniuchi, Ichiro

    2012-07-02

    Although Runx and Cbfβ transcription factor complexes are involved in the development of multiple hematopoietic lineages, their precise roles in early mouse B lymphocyte differentiation remain elusive. In this study, we examined mouse strains in which Runx1, Runx3, or Cbfβ were deleted in early B lineage progenitors by an mb1-cre transgene. Loss of Runx1, but not Runx3, caused a developmental block during early B lymphopoiesis, resulting in the lack of IgM(+) B cells and reduced V(H) to DJ(H) recombination. Expression of core transcription factors regulating early B cell development, such as E2A, Ebf1, and Pax5, was reduced in B cell precursors lacking Runx1. We detected binding of Runx1-Cbfβ complexes to the Ebf1 proximal promoter, and these Runx-binding motifs were essential to drive reporter gene expression. Runx1-deficient pro-B cells harbored excessive amounts of the repressive histone mark H3K27 trimethylation in the Ebf1 proximal promoter. Interestingly, retroviral transduction of Ebf1, but not Pax5, into Runx1-deficient progenitors restored not only development of B220(+) cells that underwent V(H) to DJ(H) rearrangement but also expression of B lineage signature genes. Collectively, these results demonstrate that Runx1-Cbfβ complexes are essential to facilitate B lineage specification, in part via epigenetic activation of the Ebf1 gene.

  9. Absolute count of T and B lymphocyte subsets is decreased in systemic sclerosis

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    Gambichler T

    2010-01-01

    Full Text Available Abstract Background Previous reports on lymphocyte subpopulations in systemic sclerosis (SSc are conflicting. Therefore, we aimed to investigate the lymphocyte subsets in SSc patients who were not on immunosuppressive therapy. Methods Lymphocyte subsets were assessed in the peripheral blood of SSc patients (n = 29 and healthy controls (n = 29 using the four colour flow cytometry method. Correlation studies were also performed in order to assess the relationship between lymphocyte subsets and clinical parameters. Results The absolute count of lymphocytes (P = 0.0042, CD3+ (P = 0.0014, CD4+ (P = 0.0070, CD8+ (P = 0.021, and CD19+ cells (P = 0.024 was significantly decreased in SSc patients when compared to healthy controls. CD4+/CD8+ ratio and the absolute count of CD56+ cells observed in SSc patients did not significantly differ from controls (P = 0.165; P = 0.632, respectively. There was no substantial relationship between the lymphocyte subset levels and clinical features (i.e., SSc subtype, autoantibody profiles, organ involvement, except for a significant inverse correlation of CD19+ cells and the modified Rodnan skin score (r = -0.43, P = 0.020. Conclusion Our data support previous reports indicating that subsets of T lymphocytes as well as B lymphocytes play a role in the pathogenesis of SSc.

  10. Enhancement of radiation induced cell death in chicken B lymphocytes by withaferin A

    International Nuclear Information System (INIS)

    Uma Devi, P.; Utsumi, H.; Takata, M.; Takeda, S.

    2008-01-01

    Withaferin A (WA), a plant withanolide, has shown significant radiosensitizing effect in vitro and in vivo. Inhibition of DNA repair has been suggested as a mechanism of radiosensitization by WA. To test this, the effect of withaferin A on survival of DT40 chicken B-lymphocyte cell line and its repair deficient single gene mutants Rad54 -/- , Ku70 -/- and double mutant Ku70 -/- /Rad54 -/- after irradiation was studied . Exponentially growing cells were treated for 1 hr with 5 μWA and then exposed to different doses of X-rays. Cell survival was studied by clonogenic assay. WA significantly reduced survival of DT40, Ku70 -/- and Ku70 -/- /Rad54 -/- , but not Rad54 -/- cells, suggesting that WA enhances radiosensitivity by interfering with homologous repair, the major pathway of DSB repair in these cells. Inhibition of DNA repair is further indicated in a significant decrease in surviving fraction of DT40 cells by post-irradiation incubation with WA. This could have relevance to cancer radiotherapy. (author)

  11. Effects of low concentrations of cadmium on immunoglobulin E production by human B lymphocytes in vitro

    International Nuclear Information System (INIS)

    Jelovcan, Sandra; Gutschi, Andrea; Kleinhappl, Barbara; Sedlmayr, Peter; Barth, Sonja; Marth, Egon

    2003-01-01

    Exposure to cadmium (Cd) can cause a variety of biological effects including alterations of immune responses in animals and humans. Both immunosuppression and immunoenhancement have been reported. The present study was aimed at investigating the consequences of exposure to Cd on the human immunoglobulin (Ig) E synthesis, using purified peripheral blood B lymphocytes and IL-4 and anti-human CD40 monoclonal antibody (a-CD40 mAb) as stimuli. Low concentrations of Cd (0.1-10 μM) markedly inhibited production of IgE in a concentration-dependent manner. IgG production, in contrast to IgE, showed a tendency towards being enhanced by Cd, although with a certain individual variability; IgM production was not affected. Cd failed to alter immediate surface expression of the activation markers CD69 and CD23 indicating that early activation events were not impaired. However, the portion of activated B cells was diminished by Cd after stimulation for more than 24 h, paralleled by a concomitant decrease in viability and a subsequent reduction in proliferation. These data suggest that the mechanism of Cd action on activated B cells involved pathways that interrupted an effectively initiated cell activation and induced a cytotoxic signal. Results from this study thus provide further evidence for and new information on the immunotoxic and immunomodulatory effects of Cd on human immune responses

  12. Rapid analysis of rearranged kappa light chain genes of circulating polysaccharide-specific B lymphocytes by means of immunomagnetic beads and the polymerase chain reaction

    DEFF Research Database (Denmark)

    Hougs, L; Barington, T; Madsen, HO

    1993-01-01

    of the B lymphocytes activated in vivo. Here, we present a method for rapid analysis of the rearranged kappa light chain genes used by human circulating antigen-specific B lymphocytes. After vaccination with Haemophilus influenzae type b capsular polysaccharide (HibCP) conjugated with protein, the Hib......Analysis of rearranged immunoglobulin genes used by B lymphocytes of known specificity is an important tool for the study of diversity and selection of B lymphocytes. Usually hybridoma cell lines are used for such analyses, but they are difficult to obtain from humans and may not be representative......CP-specific B lymphocytes were isolated by antigen-coated immunomagnetic beads. After the purification, at least 98% of the immunoglobulin-secreting recovered cells were HibCP specific. The RNA was isolated and amplified by cDNA synthesis using a kappa constant region primer followed by polymerase chain...

  13. Killer B Lymphocytes and their Fas Ligand Positive Exosomes as Inducers of Immune Tolerance

    Directory of Open Access Journals (Sweden)

    Steven Karl Lundy

    2015-03-01

    Full Text Available Induction of immune tolerance is a key process by which the immune system is educated to modulate reactions against benign stimuli such as self-antigens and commensal microbes. Understanding and harnessing the natural mechanisms of immune tolerance may become an increasingly useful strategy for treating many types of allergic and autoimmune diseases, as well as for improving the acceptance of solid organ transplants. Our laboratory and others have been interested in the natural ability of some B lymphocytes to express the death-inducing molecule Fas ligand (FasL, and their ability to kill T helper (TH lymphocytes. We have recently shown that experimental transformation of human B cells by a non-replicative variant of Epstein-Barr virus (EBV consistently resulted in high expression of functional FasL protein. The production and release of FasL+ exosomes that co-expressed MHC Class II molecules and had the capacity to kill antigen-specific TH cells was also observed. Several lines of evidence indicate that FasL+ B cells and FasL+MHCII+ exosomes have important roles in natural immune tolerance and have a great deal of therapeutic potential. Taken together, these findings suggest that EBV-immortalized human B lymphoblastoid cell lines could be used as cellular factories for FasL+ exosomes, which would be employed to therapeutically establish and/or regain immune tolerance toward specific antigens. The goals of this review are to summarize current knowledge of the roles of FasL+ B cells and exosomes in immune regulation, and to suggest methods of manipulating killer B cells and FasL+ exosomes for clinical purposes.

  14. Demonstration of binding components specific for 7,8-disubstituted guanine ribonucleosides in murine B lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    Goodman, M.G. (Research Institute of Scripps Clinic, La Jolla, CA (USA))

    1990-12-25

    7,8-Disubstituted guanine ribonucleosides are known to be potent intracellular modulators of immune responses. These compounds trigger and modulate a wide variety of lymphocyte responses including effects exerted directly on B cells. However, little is known about their mechanism of action. The current paper describes studies undertaken to evaluate whether binding components specific for these bioactive molecules exist in splenic B lymphocytes. After exposure of cells to labeled nucleoside, two different pools of nucleoside can be distinguished: a rapidly exchangeable nucleoside pool and a slowly exchangeable pool. The material in the latter pool consists of authentic unaltered nucleoside that is complexed to a relatively hydrophobic cellular component with an apparent Mr of 30,000-40,000; binding appears to interfere with free interaction of the nucleoside's cis hydroxyls with a boronate affinity resin. The slowly exchangeable nucleoside pool is seen to localize predominantly to the nucleus in electron microscopic autoradiographs. This pool is maximally bound by 30 min of incubation. Specific, saturable binding is demonstrable, with an apparent Kd of approximately 7 microM. This value correlates well with concentrations at which half-maximal biological activity occurs and suggests that the binding component likely mediates antigen-dependent immunomodulatory activity. Splenic B cells express approximately 2 x 10(4) binding sites/cell, whereas thymic lymphocytes, which do not respond functionally to nucleosides, do not display a measurable number of nucleoside binding sites. Ligand specificity of the binding interaction is confirmed by binding inhibition studies, in which binding inhibitory activity of unlabeled agonistic structural analogs recapitulate their degree of immunobiological activity.

  15. [Common variable immunodeficiency: Clinical and immunological characterization of patients and homogeneous subgroup definition by means of B lymphocyte subpopulation typing].

    Science.gov (United States)

    Vélez, Alejandra Catalina; Castaño, Diana María; Gómez, Rubén Darío; Orrego, Julio César; Moncada, Marcela; Franco, José Luis

    2015-01-01

    Common variable immunodeficiency is a heterogeneous syndrome characterized by recurrent infections, hypogammaglobulinemia and defective production of specific antibodies. Abnormalities in peripheral blood lymphocyte subpopulations, in particular of B lymphocytes, allow the classification of patients into homogeneous groups. To perform a clinical and immunological characterization and to evaluate lymphocyte subpopulations of twelve Colombian patients with common variable immunodeficiency in order to define homogeneous groups. We reviewed medical records and evaluated serum immunoglobulins (Ig), lymphoproliferation, delayed hypersensitivity and used flow cytometry to quantify peripheral blood total lymphocyte and B cell populations. All patients had recurrent respiratory and/or gastrointestinal infections, while some also had infections affecting other systems. All patients had abnormally low serum IgG levels, while IgA and IgM levels were reduced in nine and ten patients, respectively. Lymphoproliferation to mitogen was lower in patients than in healthy controls but lymphoproliferation to specific antigen was normal in all. Flow cytometry revealed high numbers of T cells in three patients, while seven had a low CD4+/CD8+ ratio and four had reduced NK cells . Eleven patients had normal B cell counts, and eight of them also showed decreased memory B lymphocytes, and four had increased transitional or CD21 low B lymphocytes. Lymphocyte typing allowed assigning all but one patient to homogeneous groups according to international classification schemes, indicating the necessity of including more criteria until an ideal classification is achieved. This study will lead to a better medical monitoring of common variable immunodeficiency patients in groups at high risk of developing clinical complications.

  16. Effects of traditional Chinese medicine Tenghuanglin on peripheral T and B lymphocyte subsets in microwave irradiated rats

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    Qiong MA

    2014-03-01

    Full Text Available Objective  To observe the effect of Tenghuanglin (THL on peripheral T and B lymphocyte subsets in microwave irradiated rats, and explore the protective effect of THL on injury to immunity induced by microwave irradiation and its mechanism. Methods  Eighty healthy male SD rats were randomly divided into 4 groups (n=20: normal control group (CON, radiation group (RAD, radiation + Anduolin (positive control drug treatment group (ADL, and radiation + THL treatment group (THL. Rats in ADL and THL groups received gavage of the individual drug once a day for 7 days, and then exposed to 30mW/cm2 microwave whole body for 15min. Rats in RAD group received same dose of microwave irradiation, and those in CON group received sham irradiation. The animals were sacrificed on 7th and 14th day after irradiation, and the changes in peripheral blood smear was observed, and CD3+, CD4+ and CD8+ T lymphocyte subsets, and CD45RA+ B lymphocyte subset were determined. Results  Fourteen days after irradiation, peripheral red blood cells in RAD group was obviously lower than those in CON, ADL and THL groups, and there was no statistically significant difference of red cell count between CON, ADL and THL groups. Seven days after irradiation, peripheral CD3+, CD4+ and CD8+ T cells in RAD group were lower in number than those in CON group, and they did not return to normal level up to 14th day. The peripheral CD3+, CD4+ and CD8+ T cells in THL and ADL groups were obviously higher than those in RAD group, and peripheral CD3+, CD4+ T cells were still higher than those in RAD group 14d after irradiation, while the peripheral CD3+, CD4+ and CD8+ T cells in THL and ADL groups were similar both at 7th and 14th day. Seven days after irradiation, the CD4/CD8 ratio was lower in RAD group than that in CON and THL groups (P<0.05, while the ratio in CON, ADL and THL groups was similar. The CD4/CD8 ratio in 4 groups was similar on 14th day after irradiation. Peripheral CD45RA+ B

  17. Switching between individual and collective motility in B lymphocytes is controlled by cell-matrix adhesion and inter-cellular interactions.

    Science.gov (United States)

    Rey-Barroso, Javier; Calovi, Daniel S; Combe, Maud; German, Yolla; Moreau, Mathieu; Canivet, Astrid; Wang, Xiaobo; Sire, Clément; Theraulaz, Guy; Dupré, Loïc

    2018-04-11

    Lymphocytes alternate between phases of individual migration across tissues and phases of clustering during activation and function. The range of lymphocyte motility behaviors and the identity of the factors that govern them remain elusive. To explore this point, we here collected unprecedented statistics pertaining to cell displacements, cell:matrix and cell:cell interactions using a model B cell line as well as primary human B lymphocytes. At low cell density, individual B lymphocytes displayed a high heterogeneity in their speed and diffusivity. Beyond this intrinsic variability, B lymphocytes adapted their motility to the composition of extra-cellular matrix, adopting slow persistent walks over collagen IV and quick Brownian walks over fibronectin. At high cell density, collagen IV favored the self-assembly of B lymphocytes into clusters endowed with collective coordination, while fibronectin stimulated individual motility. We show that this behavioral plasticity is controlled by acto-myosin dependent adhesive and Arp2/3-dependent protrusive actin pools, respectively. Our study reveals the adaptive nature of B lymphocyte motility and group dynamics, which are shaped by an interplay between and cell:matrix and cell:cell interactions.

  18. Long term effects of radiation of T and B lymphocytes in peripheral blood of patients with Hodgkin's disease

    International Nuclear Information System (INIS)

    Fuks, Z.; Strober, S.; Bobrove, A.M.; Sasazuki, T.; McMichael, A.

    1976-01-01

    Total lymphocyte counts, and the percentage of T and B lymphocytes and monocytes in untreated patients with Hodgkin's disease were not significantly different from those observed in normal donors. At the completion of radiotherapy, the mean total lymphocyte count of 503/mm3 was 4 SD below the mean for normal controls. Although a group of 26 patients in continuous complete remission from 12 to 111 months after radiation treatment regained normal total numbers of lymphocytes and monocytes, they exhibited a striking T lymphocytopenia and B lymphocytosis. Concomitantly, there was a significant increase of null (neither T nor B) lymphocytes. The response of peripheral blood lymphocytes to phytohemagglutinin, concanavalin A, and tetanus toxoid before treatment was significantly impaired. 1 to 10 yr after completion of treatment, there seemed to be little or no recovery of these responses. The capacity of peripheral blood lymphocytes to respond to allo-antigens on foreign lymphocytes in vitro (mixed lymphocyte reaction) was normal in nine untreated patients. However, the mixed lymphocyte reaction was markedly impaired during the first 2 yr after treatment. There was a partial and progressive restoration of the mixed lymphocyte reaction during the next 3 yr, and normal responses were observed in patients in continuous complete remission for 5 yr or more. The in vivo response to dinitrochlorobenzene was also examined. 88 percent (15/17) of patients initially sensitive to dinitrochlorobenzene were anergic to the allergen at the completion of a course of radiotherapy, but nine of these regained their hypersensitivity response during the 1st yr after treatment. The restoration of cell mediated immune functions after radiotherapy is time dependent and its kinetics may differ for various T-cell functions

  19. Correlation between cellular expression of complement regulatory proteins with depletion and repopulation of B-lymphocytes in peripheral blood of patients with rheumatoid arthritis treated with rituximab.

    Science.gov (United States)

    Viecceli, Daniela; Garcia, Mariana Pires; Schneider, Laiana; Alegretti, Ana Paula; Silva, Cristiano Kohler; Ribeiro, André Lucas; Brenol, Claiton Viegas; Xavier, Ricardo Machado

    To correlate the basal expression of complement regulatory proteins (CRPs) CD55, CD59, CD35, and CD46 in B-lymphocytes from the peripheral blood of a cohort of 10 patients with rheumatoid arthritis (RA) initiating treatment with rituximab (RTX) with depletion and time repopulation of such cells. Ten patients with RA received two infusions of 1g of RTX with an interval of 14 days. Immunophenotypic analysis for the detection of CD55, CD59, CD35, and CD46 on B-lymphocytes was carried out immediately before the first infusion. The population of B-lymphocytes was analyzed by means of basal CD19 expression and after 1, 2, and 6 months after the infusion of RTX, and then quarterly until clinical relapse. Depletion of B-lymphocytes in peripheral blood was defined as a CD19 expression <0.005×109/L. Ten women with a median of 49 years and a baseline DAS28=5.6 were evaluated; 9 were seropositive for rheumatoid factor. Five patients showed a repopulation of B-lymphocytes after 2 months, and the other five after 6 months. There was a correlation between the basal expression of CD46 and the time of repopulation (correlation coefficient=-0.733, p=0.0016). A similar trend was observed with CD35, but without statistical significance (correction coefficient=-0.522, p=0.12). The increased CD46 expression was predictive of a faster repopulation of B-lymphocytes in patients treated with RTX. Studies involving a larger number of patients will be needed to confirm the utility of basal expression of CRPs as a predictor of clinical response. Copyright © 2016 Elsevier Editora Ltda. All rights reserved.

  20. Rapid analysis of rearranged kappa light chain genes of circulating polysaccharide-specific B lymphocytes by means of immunomagnetic beads and the polymerase chain reaction

    DEFF Research Database (Denmark)

    Hougs, L; Barington, T; Madsen, HO

    1993-01-01

    -secreting cells. Examples of rearranged kappa genes used by HibCP-specific antibody-secreting cells from 4 adult vaccinees are given, representing the 3 largest of the 4 kappa variable region families. This method is a new tool for the investigation of vaccine-induced antibody responses with special reference...... of the B lymphocytes activated in vivo. Here, we present a method for rapid analysis of the rearranged kappa light chain genes used by human circulating antigen-specific B lymphocytes. After vaccination with Haemophilus influenzae type b capsular polysaccharide (HibCP) conjugated with protein, the Hib...

  1. Liver-X-receptor activator prevents homocysteine-induced production of IgG antibodies from murine B lymphocytes via the ROS-NF-κB pathway

    International Nuclear Information System (INIS)

    Chang Lina; Zhang, Zhenmin; Li Wenjing; Dai Jing; Guan Youfei; Wang Xian

    2007-01-01

    Our previous study showed that homosysteine (Hcy) promotes proliferation of mouse splenic B lymphocytes. In this study, we investigated whether Hcy could stimulate the production of IgG antibodies. Hcy significantly increased the production of IgG antibodies from resting B lymphocytes. B lymphocytes from ApoE-knockout mice with hyperhomocysteinemia showed elevated IgG secretion at either the basal Hcy level or in response to lipopolysaccharide. Hcy promoted reactive oxygen species (ROS) formation, and free radical scavengers, MnTMPyP decreased Hcy-induced IgG secretion. The inhibitor of NF-κB (MG132) also significantly reduced Hcy-induced IgG secretion. Furthermore, Hcy-induced formation of ROS, activation of NF-κB, and secretion of IgG could be inhibited by the liver-X-receptor (LXR) agonist TO 901317. Thus, our data provide strong evidence that HHcy induces IgG production from murine splenic B lymphocytes both in vitro and in vivo. The mechanism might be through the ROS-NF-κB pathway and can be attenuated by the activation of LXR

  2. The rationale for B lymphocyte depletion in Graves' disease. Monoclonal anti-CD20 antibody therapy as a novel treatment option

    DEFF Research Database (Denmark)

    El Fassi, Daniel; Nielsen, Claus H; Hasselbalch, Hans K

    2006-01-01

    We have reviewed the immunology of thyroid autoimmunity with special reference to the importance of B lymphocytes (B cells) in thyroidal and extrathyroidal Graves' disease (GD), thus providing a framework for the hypothesis that B cell depletion may be beneficial in GD. Additionally, after...

  3. Triptolide inhibits proliferation of Epstein–Barr virus-positive B lymphocytes by down-regulating expression of a viral protein LMP1

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Heng [Department of Pathogen Biology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071 (China); Guo, Wei [Department of Pathology and Physiology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071 (China); Long, Cong; Wang, Huan; Wang, Jingchao [Department of Pathogen Biology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071 (China); Sun, Xiaoping, E-mail: xsun6@whu.edu.cn [Department of Pathogen Biology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071 (China); State Key Laboratory of Virology, Wuhan University, Wuhan 430072 (China)

    2015-01-16

    Highlights: • Triptolide inhibits proliferation of EBV-positive lymphoma cells in vitro and in vivo. • Triptolide reduces expression of LMP1 by decreasing its transcription level. • Triptolide inhibits ED-L1 promoter activity. - Abstract: Epstein–Barr virus (EBV) infects various types of cells and mainly establishes latent infection in B lymphocytes. The viral latent membrane protein 1 (LMP1) plays important roles in transformation and proliferation of B lymphocytes infected with EBV. Triptolide is a compound of Tripterygium extracts, showing anti-inflammatory, immunosuppressive, and anti-cancer activities. In this study, it is determined whether triptolide inhibits proliferation of Epstein–Barr virus-positive B lymphocytes. The CCK-8 assays were performed to examine cell viabilities of EBV-positive B95-8 and P3HR-1 cells treated by triptolide. The mRNA and protein levels of LMP1 were examined by real time-PCR and Western blotting, respectively. The activities of two LMP1 promoters (ED-L1 and TR-L1) were determined by Dual luciferase reportor assay. The results showed that triptolide inhibited the cell viability of EBV-positive B lymphocytes, and the over-expression of LMP1 attenuated this inhibitory effect. Triptolide decreased the LMP1 expression and transcriptional levels in EBV-positive B cells. The activity of LMP1 promoter ED-L1 in type III latent infection was strongly suppressed by triptolide treatment. In addition, triptolide strongly reduced growth of B95-8 induced B lymphoma in BALB/c nude mice. These results suggest that triptolide decreases proliferation of EBV-induced B lymphocytes possibly by a mechanism related to down-regulation of the LMP1 expression.

  4. Influence of prevaccination immunity on the human B-lymphocyte response to a Haemophilus influenzae type b conjugate vaccine

    DEFF Research Database (Denmark)

    Barington, T; Kristensen, K; Henrichsen, J

    1991-01-01

    of Haemophilus influenzae type b capsular polysaccharide (PRP) and diphtheria toxoid (DT), and the response was related to the prevaccination levels of PRP and DT antibodies. Positive correlations were found between increases in plasma PRP (median, 32.0 micrograms/ml) and DT (1.14 IU/ml) antibodies and numbers......The purpose of this study was to investigate whether preexisting immunity to components of a polysaccharide-protein conjugate influences the B-lymphocyte response to vaccination with the conjugate. Thirty-two healthy adults were vaccinated once or twice with a conjugate (PRP-D) consisting...... of circulating PRP and DT antibody-secreting cells (AbSC) (postvaccination days 6 to 9). The B-cell responses (antibody response and AbSC) to both PRP and DT correlated positively with prevaccination levels of anti-DT. DT AbSC appeared earlier (peak, day 7) than PRP AbSC (peak, day 8). Individuals whose PRP Ab...

  5. Runx1–Cbfβ facilitates early B lymphocyte development by regulating expression of Ebf1

    Science.gov (United States)

    Seo, Wooseok; Ikawa, Tomokatsu; Kawamoto, Hiroshi

    2012-01-01

    Although Runx and Cbfβ transcription factor complexes are involved in the development of multiple hematopoietic lineages, their precise roles in early mouse B lymphocyte differentiation remain elusive. In this study, we examined mouse strains in which Runx1, Runx3, or Cbfβ were deleted in early B lineage progenitors by an mb1-cre transgene. Loss of Runx1, but not Runx3, caused a developmental block during early B lymphopoiesis, resulting in the lack of IgM+ B cells and reduced VH to DJH recombination. Expression of core transcription factors regulating early B cell development, such as E2A, Ebf1, and Pax5, was reduced in B cell precursors lacking Runx1. We detected binding of Runx1–Cbfβ complexes to the Ebf1 proximal promoter, and these Runx-binding motifs were essential to drive reporter gene expression. Runx1-deficient pro-B cells harbored excessive amounts of the repressive histone mark H3K27 trimethylation in the Ebf1 proximal promoter. Interestingly, retroviral transduction of Ebf1, but not Pax5, into Runx1-deficient progenitors restored not only development of B220+ cells that underwent VH to DJH rearrangement but also expression of B lineage signature genes. Collectively, these results demonstrate that Runx1–Cbfβ complexes are essential to facilitate B lineage specification, in part via epigenetic activation of the Ebf1 gene. PMID:22665574

  6. Novel Strategy for Phenotypic Characterization of Human B Lymphocytes from Precursors to Effector Cells by Flow Cytometry.

    Directory of Open Access Journals (Sweden)

    Giovanna Clavarino

    Full Text Available A precise identification and phenotypic characterization of human B-cell subsets is of crucial importance in both basic research and medicine. In the literature, flow cytometry studies for the phenotypic characterization of B-lymphocytes are mainly focused on the description of a particular cell stage, or of specific cell stages observed in a single type of sample. In the present work, we propose a backbone of 6 antibodies (CD38, CD27, CD10, CD19, CD5 and CD45 and an efficient gating strategy to identify, in a single analysis tube, a large number of B-cell subsets covering the whole B-cell differentiation from precursors to memory and plasma cells. Furthermore, by adding two antibodies in an 8-color combination, our approach allows the analysis of the modulation of any cell surface marker of interest along B-cell differentiation. We thus developed a panel of seven 8-colour antibody combinations to phenotypically characterize B-cell subpopulations in bone marrow, peripheral blood, lymph node and cord blood samples. Beyond qualitative information provided by biparametric representations, we also quantified antigen expression on each of the identified B-cell subsets and we proposed a series of informative curves showing the modulation of seventeen cell surface markers along B-cell differentiation. Our approach by flow cytometry provides an efficient tool to obtain quantitative data on B-cell surface markers expression with a relative easy-to-handle technique that can be applied in routine explorations.

  7. Water Oxygen Content Affects Distribution of T and B Lymphocytes in Lymphoid Tissues of Farmed Sea Bass (Dicentrarchus Labrax

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    Nicla Romano

    2017-09-01

    Full Text Available Intensive aquaculture systems have stimulated proper management in order to limit stressful stocking conditions and environmental impact. This should improve fish wellness and counteract adverse water characteristics such as high concentrations of carbon. The oxygen can be considered a key factor since critical conditions leading to chronic rise of blood catecholamines can depress the number and Oxygen-carrying capacity of erythrocytes. In this research, we evaluated the effects of variation in water oxygen (from 6 ± 1 to 13 ± 1 mg/L on lymphocytes density in sea bass by using flow cytometry and immunohistochemistry. Gut, gill, and thymus T-cells were significantly enhanced in percentage in hyperoxygenated fish compared with normo-oxygenated group, while Peripheral Blood Leukocytes (PBL, head kidney, and spleen T-cells were not significantly different. Contrarily, in PBL, head kidney and spleen hyper-oxygenation treatment provoked an enhancement of B lymphocyte percentages. The distribution of positive T-cells in hyper-oxygenated fish varied in the organs and followed the relative increments/decrements observed in flow cytometry. This study remarks the sensitivity of sea bass adaptive immunocytes to oxygen concentration, evidenced by the modification of parameters. Sea bass culture under high-flow water recycling and at around 12–13 mg/L oxygen concentrations is therefore suggested to enhance the immune response capacity.

  8. B-Lymphocytes from a Population of Children with Autism Spectrum Disorder and Their Unaffected Siblings Exhibit Hypersensitivity to Thimerosal

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    Martyn A. Sharpe

    2013-01-01

    Full Text Available The role of thimerosal containing vaccines in the development of autism spectrum disorder (ASD has been an area of intense debate, as has the presence of mercury dental amalgams and fish ingestion by pregnant mothers. We studied the effects of thimerosal on cell proliferation and mitochondrial function from B-lymphocytes taken from individuals with autism, their nonautistic twins, and their nontwin siblings. Eleven families were examined and compared to matched controls. B-cells were grown with increasing levels of thimerosal, and various assays (LDH, XTT, DCFH, etc. were performed to examine the effects on cellular proliferation and mitochondrial function. A subpopulation of eight individuals (4 ASD, 2 twins, and 2 siblings from four of the families showed thimerosal hypersensitivity, whereas none of the control individuals displayed this response. The thimerosal concentration required to inhibit cell proliferation in these individuals was only 40% of controls. Cells hypersensitive to thimerosal also had higher levels of oxidative stress markers, protein carbonyls, and oxidant generation. This suggests certain individuals with a mild mitochondrial defect may be highly susceptible to mitochondrial specific toxins like the vaccine preservative thimerosal.

  9. B lymphocytes and macrophages release cell membrane deposited C3-fragments on exosomes with T cell response-enhancing capacity.

    Science.gov (United States)

    Papp, Krisztián; Végh, Péter; Prechl, József; Kerekes, Krisztina; Kovács, János; Csikós, György; Bajtay, Zsuzsa; Erdei, Anna

    2008-04-01

    Recently exosomes have been shown to play important roles in several immune phenomena. These small vesicles contain MHC proteins along with co-stimulatory and adhesion molecules, and mediate antigen presentation to T cells. In the present study we show that upon incubation with autologous serum, murine macrophages and B cells--but not T lymphocytes--fix C3-fragments covalently to the cell membrane and release them on exosomes in a time dependent fashion. While in the case of human B lymphocytes CR2 has been shown to serve as the main C3b-acceptor site, here we clearly demonstrate that cells derived from CR1/2 KO animals also have the capacity to fix C3b covalently. This finding points to a major difference between human and murine systems, and suggests the existence of additional acceptor sites on the cell membrane. Here we show that C3-fragment containing exosomes derived from OVA loaded antigen presenting cells induce a significantly elevated T cell response in the presence of suboptimal antigen stimulus. These data reveal a novel function of cell surface-deposited C3-fragments and provide further evidence for the role of exosomes secreted by antigen presenting cells. Since fixation of C3b to plasma membranes can be substantial in the presence of pathogens; moreover tumor cells are also known to activate the complement system resulting in complement-deposition, C3-carrying exosomes released by these cells may play an important immunomodulatory role in vivo, as well.

  10. Cerebrospinal Fluid B-lymphocyte Chemoattractant CXCL13 in the Diagnosis of Acute Lyme Neuroborreliosis in Children.

    Science.gov (United States)

    Barstad, Bjørn; Tveitnes, Dag; Noraas, Sølvi; Selvik Ask, Ingvild; Saeed, Maryam; Bosse, Franziskus; Vigemyr, Grete; Huber, Ilka; Øymar, Knut

    2017-12-01

    Current markers of Lyme neuroborreliosis (LNB) in children have insufficient sensitivity in the early stage of disease. The B-lymphocyte chemoattractant CXCL13 in the cerebrospinal fluid (CSF) may be useful in diagnosing LNB, but its specificity has not been evaluated in studies including children with clinically relevant differential diagnoses. The aim of this study was to elucidate the diagnostic value of CSF CXCL13 in children with symptoms suggestive of LNB. Children with symptoms suggestive of LNB were included prospectively into predefined groups with a high or low likelihood of LNB based on CSF pleocytosis and the detection of Borrelia antibodies or other causative agents. CSF CXCL13 levels were compared between the groups, and receiver-operating characteristic analyses were performed to indicate optimal cutoff levels to discriminate LNB from non-LNB conditions. Two hundred and ten children were included. Children with confirmed LNB (n=59) and probable LNB (n=18) had higher CSF CXCL13 levels than children with possible LNB (n=7), possible peripheral LNB (n=7), non-Lyme aseptic meningitis (n=12), non-meningitis (n=91) and negative controls (n=16). Using 18 pg/mL as a cutoff level, both the sensitivity and specificity of CSF CXCL13 for LNB (confirmed and probable) were 97%. Comparing only children with LNB and non-Lyme aseptic meningitis, the sensitivity and specificity with the same cutoff level were 97% and 83%, respectively. CSF CXCL13 is a sensitive marker of LNB in children. The specificity to discriminate LNB from non-Lyme aseptic meningitis may be more moderate, suggesting that CSF CXCL13 should be used together with other variables in diagnosing LNB in children.

  11. Macropinocytosis is responsible for the uptake of pathogenic and non-pathogenic mycobacteria by B lymphocytes (Raji cells

    Directory of Open Access Journals (Sweden)

    García-Pérez Blanca Estela

    2012-10-01

    Full Text Available Abstract Background The classical roles of B cells include the production of antibodies and cytokines and the generation of immunological memory, these being key factors in the adaptive immune response. However, their role in innate immunity is currently being recognised. Traditionally, B cells have been considered non-phagocytic cells; therefore, the uptake of bacteria by B cells is not extensively documented. In this study, we analysed some of the features of non-specific bacterial uptake by B lymphocytes from the Raji cell line. In our model, B cells were infected with Mycobacterium tuberculosis (MTB, Mycobacterium smegmatis (MSM, and Salmonella typhimurium (ST. Results Our observations revealed that the Raji B cells were readily infected by the three bacteria that were studied. All of the infections induced changes in the cellular membrane during bacterial internalisation. M. smegmatis and S. typhimurium were able to induce important membrane changes that were characterised by abundant filopodia and lamellipodia formation. These membrane changes were driven by actin cytoskeletal rearrangements. The intracellular growth of these bacteria was also controlled by B cells. M. tuberculosis infection also induced actin rearrangement-driven membrane changes; however, the B cells were not able to control this infection. The phorbol 12-myristate 13-acetate (PMA treatment of B cells induced filopodia and lamellipodia formation, the production of spacious vacuoles (macropinosomes, and the fluid-phase uptake that is characteristic of macropinocytosis. S. typhimurium infection induced the highest fluid-phase uptake, although both mycobacteria also induced fluid uptake. A macropinocytosis inhibitor such as amiloride was used and abolished the bacterial uptake and the fluid-phase uptake that is triggered during the bacterial infection. Conclusions Raji B cells can internalise S. typhimurium and mycobacteria through an active process, such as

  12. Modulation of B lymphocyte function by an aqueous fraction of the ethanol extract of Cissampelos sympodialis Eichl (Menispermaceae

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    M.S. Alexandre-Moreira

    2003-11-01

    Full Text Available Cissampelos sympodialis Eichl species are used in folk medicine for the treatment of asthma, arthritis and rheumatism. In the present study, we investigated the immunomodulatory effect of an aqueous fraction of a 70% (v/v ethanol extract of C. sympodialis leaves on B lymphocyte function. The hydroalcoholic extract inhibited the in vitro proliferative response of resting B cells induced by LPS (IC50 = 17.2 µg/ml, anti-delta-dextran (IC50 = 13.9 µg/ml and anti-IgM (IC50 = 24.3 µg/ml but did not affect the anti-MHC class II antibody-stimulated proliferative response of B cell blasts obtained by stimulation with IL-4 and anti-IgM. Incubation with the hydroalcoholic extract used at 50 µg/ml induced a 700% increase in intracellular cAMP levels. IgM secretion by resting B cells (obtained from normal mice and polyclonally activated B cells (obtained from Trypanosoma cruzi-infected animals was inhibited by the hydroalcoholic extract. The latter were more sensitive to the hydroalcoholic extract since 6.5 µg/ml induced a 20% inhibition in the response of cells from normal mice while it inhibited the response of B cells from infected animals by 75%. The present data indicate that the alcoholic extract of C. sympodialis inhibited B cell function through an increase in intracellular cAMP levels. The finding that the hydroalcoholic extract inhibited immunoglobulin secretion suggests a therapeutic use for the extract from C. sympodialis in conditions associated with unregulated B cell function and enhanced immunoglobulin secretion. Finally, the inhibitory effect of the hydroalcoholic extract on B cells may indicate an anti-inflammatory effect of this extract.

  13. Alterations in Sensitivity to Estrogen, Dihydrotestosterone, and Xenogens in B-Lymphocytes from Children with Autism Spectrum Disorder and Their Unaffected Twins/Siblings

    OpenAIRE

    Martyn A. Sharpe; Taylor L. Gist; David S. Baskin

    2013-01-01

    It has been postulated that androgen overexposure in a susceptible person leads to excessive brain masculinization and the autism spectrum disorder (ASD) phenotype. In this study, the responses to estradiol (E2), dihydrotestosterone (DHT), and dichlorodiphenyldichloroethylene (DDE) on B-lymphocytes from ASD subjects and controls are compared. B cells were obtained from 11 ASD subjects, their unaffected fraternal twins, and nontwin siblings. Controls were obtained from a different cell bank. L...

  14. Development of an in vitro system to assess the effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin on B lymphocyte activation and differentiation

    International Nuclear Information System (INIS)

    Clark, G.C. Jr.

    1988-01-01

    Humoral immunity appears to be a sensitive target for chemical induced immunosuppression. Therefore, in vitro methodologies were developed to assess the effects of environmental chemicals on B lymphocyte activation and differentiation. The environmental chemical, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was used to develop these methodologies. The in vitro humoral immune response of purified B cells to the T-independent antigen TNP-LPS was suppressed in a dose dependent manner with an EC 50 of 10 nM TCDD. A polyclonal activation system using anti-immunoglobulin and T cell derived factors was used to further analyze B lymphocyte suppression by TCDD. The activation and proliferation responses of B lymphocytes were not affected by TCDD as monitored by the incorporation of 3 H-uridine and 3 H-thymidine or expression of the cell surface markers Ia and the IL-2 receptor. Terminal differentiation was selectively inhibited by TCDD as assessed by a dose dependent inhibition of immunoglobulin synthesis and expression of the cell surface marker PC.2. Protein phosphorylation, an early event in lymphocyte activation, was altered by exposure to TCDD and was associated with a dose dependent increase in the activity of tyrosine-specific protein kinases

  15. Alterations in Sensitivity to Estrogen, Dihydrotestosterone, and Xenogens in B-Lymphocytes from Children with Autism Spectrum Disorder and Their Unaffected Twins/Siblings

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    Martyn A. Sharpe

    2013-01-01

    Full Text Available It has been postulated that androgen overexposure in a susceptible person leads to excessive brain masculinization and the autism spectrum disorder (ASD phenotype. In this study, the responses to estradiol (E2, dihydrotestosterone (DHT, and dichlorodiphenyldichloroethylene (DDE on B-lymphocytes from ASD subjects and controls are compared. B cells were obtained from 11 ASD subjects, their unaffected fraternal twins, and nontwin siblings. Controls were obtained from a different cell bank. Lactate dehydrogenase (LDH and sodium 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl-2H-tetrazolium-5-carboxanilide (XTT reduction levels were measured after incubation with different concentrations of E2, DHT, and DDE. XTT/LDH ratio, representative of mitochondria number per cell, was calculated. E2, DHT, and DDE all cause “U”-shaped growth curves, as measured by LDH levels. ASD B cells show less growth depression compared to siblings and controls (P<0.01. They also have reduced XTT/LDH ratios (P<0.01 when compared to external controls, whereas siblings had values of XTT/LDH between ASD and external controls. B-lymphocytes from people with ASD exhibit a differential response to E2, DHT, and hormone disruptors in regard to cell growth and mitochondrial upregulation when compared to non-ASD siblings and external controls. Specifically, ASD B-lymphocytes show significantly less growth depression and less mitochondrial upregulation when exposed to these effectors. A mitochondrial deficit in ASD individuals is implied.

  16. A complex relationship between TRAF3 and non-canonical NF-κB2 activation in B lymphocytes

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    Wai Wai Lin

    2013-12-01

    Full Text Available The adaptor protein TRAF3 restrains BAFF receptor (BAFFR and CD40-mediated activation of the NF-κB2 pathway in B cells. Mice lacking TRAF3 specifically in B cells revealed the critical role of TRAF3 in restraining homeostatic B cell survival. Furthermore, loss- of-function mutations of the traf3 gene have been associated with human B cell malignancies, especially multiple myeloma (MM. It has been proposed that receptor-induced TRAF3 degradation leads to stabilization of the NF-B inducing kinase NIK, and subsequent NF-κB2 activation. However, it is unclear how receptor-mediated TRAF3 degradation or loss of function contributes to B cell-specific NF-κB2 activation. In the current study, we employed two complementary models to address this question. One utilized a mutant traf3 gene found in a human MM-derived cell line called LP1. The LP1 mutant TRAF3 protein lacks the TRAF-N and TRAF-C domains. Consistent with the paradigm described, expression of LP1 TRAF3 in B cells promoted higher basal levels of NF-κB2 activation compared to Wt TRAF3. However, LP1 did not associate with TRAF2, CD40, or BAFFR, and no LP1 degradation was observed following receptor engagement. Interestingly, LP1 showed enhanced NIK association. Thus, TRAF3 degradation becomes dispensable to activate NF-κB2 when it is unable to associate with TRAF2. In a second model, we examined several mutant forms of BAFFR that are unable to induce NF-κB2 activation in B cells. Signaling to B cells by each of these BAFFR mutants, however, induced levels of TRAF3 degradation similar to those induced by Wt BAFFR. Thus, in B cells, receptor-mediated TRAF3 degradation is not sufficient to promote NF-B2 activation. We thus conclude that there is not a simple linear relationship in B lymphocytes between relative levels of cellular TRAF3, induced TRAF3 degradation, NIK activation and NF-B2 activation.

  17. Modulating effect of the piperine, the main alkaloid from Piper nigrum Linn., on murine B lymphocyte function

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    Aline Rodrigues Bernardo

    2015-10-01

    Full Text Available ABSTRACT. Bernardo A.R., da Rocha J.D.B., de Lima M.E.F., Decote-Ricardo D., Pinto-da-Silva L.H., Peçanha L.M.T. & Danelli M. dasG.M. Modulating effect of the piperine, the main alkaloid from Piper nigrum Linn., on murine B lymphocyte function. [Efeito modulador da piperina, principal alcalóide da Piper nigrum Linn., sobre a função de linfócitos B murinos.] Revista Brasileira de Medicina Veterinária, 37(3:209-216, 2015. Departamento de Microbiologia e Imunologia Veterinária, Instituto de Veterinária, Universidade Federal Rural de Janeiro, Campus Seropédica, BR 465 Km 7, Seropédica, RJ 23890-000, Brazil. E-mail: danelli @ufrrj.br Piperine is the main alkaloid of black and long peppers and it is conventionally used as immune-enhancers in Indian system of traditional medicine. The main of this study was evaluated for the first time the effect of piperine on B cells functions in vitro and its effects on humoral immune response to T-dependent and T-independent antigens. Different concentrations of piperine (1 µM, 3 µM and 15 µM were assayed on B cells purified from BALB/c spleen cells and evaluated its effects on proliferation, IgM secretion and expression of CD86 on murine B cells. At 15 µM piperine was able to inhibit the proliferative response induced by LPS and α-IgM antibody and inhibited the secretion IgM antibody in vitro. Also, piperine at 3 µM and 15 µM reduced the CD86 expression on B cells stimulated with LPS and α-IgM antibody in vitro. However, piperine 2.5 and 4.5 mg/Kg did not modulated antibody production for T-independet (TNP-Ficoll in vivo.

  18. Peripheral blood B lymphocytes derived from patients with idiopathic pulmonary arterial hypertension express a different RNA pattern compared with healthy controls: a cross sectional study

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    Huber Lars C

    2008-02-01

    Full Text Available Abstract Background Idiopathic pulmonary arterial hypertension (IPAH is a progressive and still incurable disease. Research of IPAH-pathogenesis is complicated by the lack of a direct access to the involved tissue, the human pulmonary vasculature. Various auto-antibodies have been described in the blood of patients with IPAH. The purpose of the present work was therefore to comparatively analyze peripheral blood B lymphocyte RNA expression characteristics in IPAH and healthy controls. Methods Patients were diagnosed having IPAH according to WHO (mean pulmonary arterial pressure ≥ 25 mmHg, pulmonary capillary occlusion pressure ≤ 15 mmHg, absence of another explaining disease. Peripheral blood B-lymphocytes of patients and controls were immediately separated by density gradient centrifugation and magnetic beads for CD19. RNA was thereafter extracted and analyzed by the use of a high sensitivity gene chip (Affymetrix HG-U133-Plus2 able to analyze 47000 transcripts and variants of human genes. The array data were analyzed by two different softwares, and up-and down-regulations were defined as at least 1.3 fold with standard deviations smaller than fold-changes. Results Highly purified B-cells of 5 patients with IPAH (mean pulmonary artery pressure 51 ± 13 mmHg and 5 controls were analyzed. Using the two different analyzing methods we found 225 respectively 128 transcripts which were up-regulated (1.3–30.7 fold in IPAH compared with healthy controls. Combining both methods, there were 33 overlapping up-regulated transcripts and no down-regulated B-cell transcripts. Conclusion Patients with IPAH have a distinct RNA expression profile of their peripheral blood B-lymphocytes compared to healthy controls with some clearly up-regulated genes. Our finding suggests that in IPAH patients B cells are activated.

  19. Phosphodiesterase profile of human B lymphocytes from normal and atopic donors and the effects of PDE inhibition on B cell proliferation

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    Gantner, Florian; Götz, Christine; Gekeler, Volker; Schudt, Christian; Wendel, Albrecht; Hatzelmann, Armin

    1998-01-01

    CD19+ B lymphocytes were purified from the peripheral blood of normal and atopic subjects to analyse and compare the phosphodiesterase (PDE) activity profile, PDE mRNA expression and the importance of PDE activity for the regulation of B cell function.The majority of cyclic AMP hydrolyzing activity of human B cells was cytosolic PDE4, followed by cytosolic PDE7-like activity; marginal PDE3 activity was found only in the particulate B cell fraction. PDE1, PDE2 and PDE5 activities were not detected.By cDNA-PCR analysis mRNA of the PDE4 subtypes A, B (splice variant PDE4B2) and D were detected. In addition, a weak signal for PDE3A was found.No differences in PDE activities or mRNA expression of PDE subtypes were found in B cells from either normal or atopic subjects.Stimulation of B lymphocytes with the polyclonal stimulus lipopolysaccharide (LPS) induced a proliferative response in a time- and concentration-dependent manner, which was increased in the presence of interleukin-4 (IL-4). PDE4 inhibitors (rolipram, piclamilast) led to an increase in the cellular cyclic AMP concentration and to an augmentation of proliferation, whereas a PDE3 inhibitor (motapizone) was ineffective, which is in accordance with the PDE profile found. The proliferation enhancing effect of the PDE4 inhibitors was partly mimicked by the cyclic AMP analogues dibutyryl (db) cyclic AMP and 5,6-dichloro-1-β-D-ribofuranosylbenzimidazole-3′,5′-cyclic monophosphorothioate, Sp-isomer (dcl-cBIMPS), respectively. However, at concentrations exceeding 100 μM db-cyclic AMP suppressed B lymphocyte proliferation, probably as a result of cytotoxicity. Prostaglandin E2 (PGE2, 1 μM) and forskolin (10 μM) did not affect B cell proliferation, even when given in combination with rolipram.Inhibition of protein kinase A (PKA) by differentially acting selective inhibitors (KT 5720, Rp-8-Br-cyclic AMPS) decreased the proliferative response of control cells and reversed the proliferation enhancing effects

  20. The potential impact of low dose ionizing γ-radiation on immune response activity up-regulated by Ikaros in IM-9 B lymphocytes

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    Kim Sung Jn; Jang, Seon A; Yang, Kwang Hee; Kim, Ji Young; Kim, Cha Soon; Nam, Seon Young; Jeong, Mee Seon; Jin, Young Woo [Radiation Health Research Institute, Korea Hydro and Nuclear Power Co., LTD, Seoul (Korea, Republic of)

    2011-11-15

    The biological effects of low dose ionizing radiation (LDIR) remain insufficiently understood. We examined for the scientific evidence to show the biological effects of LDIR using radiation-sensitive immune cells. We found that Ikaros protein was responded to low dose-dependent effects of gamma radiation in IM-9 B lymphocytes. Ikaros encodes zinc finger transcription factors that is important regulators of a hematopoietic stem cells (HSCs) progression to the B lymphoid lineage development, differentiation and proliferation. In this study, we observed that cell proliferation was enhanced from 10% to 20% by LDIR (0.05 Gy) in IM-9 B lymphocytes. The Ikaros protein was phosphorylated in its serine/threonine (S/T) region and decreased its DNA binding activity in the cells exposed to LDIR. We found that Ikaros phosphorylation was up-regulated by CK2/AKT pathway and the residues of ser-304 and ser-306 in Ikaros was phosphorylated by LDIR. We also observed that Ikaros protein was localized from the nucleus to the cytoplasm after LDIR and bound with Autotaxin (ENPP2, ATX) protein, stimulating proliferation, migration and survival of immune cells. In addition, we found that the lysoPLD activity of ATX was dependent on Ikaros-ATX binding activity. These results indicate that the Ikaros is an important regulator of immune activation. Therefore, we suggest that low dose ionizing radiation can be considered as a beneficial effects, stimulating the activation of immune cells.

  1. Myosin 1g Contributes to CD44 Adhesion Protein and Lipid Rafts Recycling and Controls CD44 Capping and Cell Migration in B Lymphocytes

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    Orestes López-Ortega

    2017-12-01

    Full Text Available Cell migration and adhesion are critical for immune system function and involve many proteins, which must be continuously transported and recycled in the cell. Recycling of adhesion molecules requires the participation of several proteins, including actin, tubulin, and GTPases, and of membrane components such as sphingolipids and cholesterol. However, roles of actin motor proteins in adhesion molecule recycling are poorly understood. In this study, we identified myosin 1g as one of the important motor proteins that drives recycling of the adhesion protein CD44 in B lymphocytes. We demonstrate that the lack of Myo1g decreases the cell-surface levels of CD44 and of the lipid raft surrogate GM1. In cells depleted of Myo1g, the recycling of CD44 was delayed, the delay seems to be caused at the level of formation of recycling complex and entry into recycling endosomes. Moreover, a defective lipid raft recycling in Myo1g-deficient cells had an impact both on the capping of CD44 and on cell migration. Both processes required the transportation of lipid rafts to the cell surface to deliver signaling components. Furthermore, the extramembrane was essential for cell expansion and remodeling of the plasma membrane topology. Therefore, Myo1g is important during the recycling of lipid rafts to the membrane and to the accompanied proteins that regulate plasma membrane plasticity. Thus, Myosin 1g contributes to cell adhesion and cell migration through CD44 recycling in B lymphocytes.

  2. Effects of atomic bomb radiation on differentiation of B lymphocytes and on the function of concanavalin A-induced suppressor T lymphocytes

    International Nuclear Information System (INIS)

    Yamada, Y.; Neriishi, S.; Ishimaru, T.; Shimba, N.; Hamilton, H.B.; Ohgushi, Y.; Koyanagi, M.; Ichimaru, M.

    1985-01-01

    The differentiation of peripheral blood B lymphocytes into immunoglobulin-producing cells (Ig-PC) by pokeweed mitogen (PWM) and the function of concanavalin A (Con A)-induced suppressor T lymphocytes were examined to elucidate the late effects of atomic bomb radiation. A total of 140 individuals, 70 with an exposure dose of 100 rad or more and an equal number with an exposure dose of 0 rad matched by sex and age, were selected from the Nagasaki Adult Health Study (AHS) sample. Both the differentiation of peripheral blood B lymphocytes into Ig-PC by PWM and the function of Con A-induced suppressor T lymphocytes tended to be more depressed in the exposed group than in the control group, but a statistically significant difference could not be observed between the two groups. The function of Con A-induced suppressor T lymphocytes tended to decrease with age, but a statistical significance was detected only for percentage suppression against IgM-PC

  3. The potential impact of low dose ionizing γ-radiation on immune response activity up-regulated by Ikaros in IM-9 B lymphocytes

    International Nuclear Information System (INIS)

    Kim Sung Jn; Jang, Seon A; Yang, Kwang Hee; Kim, Ji Young; Kim, Cha Soon; Nam, Seon Young; Jeong, Mee Seon; Jin, Young Woo

    2011-01-01

    The biological effects of low dose ionizing radiation (LDIR) remain insufficiently understood. We examined for the scientific evidence to show the biological effects of LDIR using radiation-sensitive immune cells. We found that Ikaros protein was responded to low dose-dependent effects of gamma radiation in IM-9 B lymphocytes. Ikaros encodes zinc finger transcription factors that is important regulators of a hematopoietic stem cells (HSCs) progression to the B lymphoid lineage development, differentiation and proliferation. In this study, we observed that cell proliferation was enhanced from 10% to 20% by LDIR (0.05 Gy) in IM-9 B lymphocytes. The Ikaros protein was phosphorylated in its serine/threonine (S/T) region and decreased its DNA binding activity in the cells exposed to LDIR. We found that Ikaros phosphorylation was up-regulated by CK2/AKT pathway and the residues of ser-304 and ser-306 in Ikaros was phosphorylated by LDIR. We also observed that Ikaros protein was localized from the nucleus to the cytoplasm after LDIR and bound with Autotaxin (ENPP2, ATX) protein, stimulating proliferation, migration and survival of immune cells. In addition, we found that the lysoPLD activity of ATX was dependent on Ikaros-ATX binding activity. These results indicate that the Ikaros is an important regulator of immune activation. Therefore, we suggest that low dose ionizing radiation can be considered as a beneficial effects, stimulating the activation of immune cells.

  4. The loss of Gnai2 and Gnai3 in B cells eliminates B lymphocyte compartments and leads to a hyper-IgM like syndrome.

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    Il-Young Hwang

    Full Text Available B lymphocytes are compartmentalized within lymphoid organs. The organization of these compartments depends upon signaling initiated by G-protein linked chemoattractant receptors. To address the importance of the G-proteins Gαi2 and Gαi3 in chemoattractant signaling we created mice lacking both proteins in their B lymphocytes. While bone marrow B cell development and egress is grossly intact; mucosal sites, splenic marginal zones, and lymph nodes essentially lack B cells. There is a partial block in splenic follicular B cell development and a 50-60% reduction in splenic B cells, yet normal numbers of splenic T cells. The absence of Gαi2 and Gαi3 in B cells profoundly disturbs the architecture of lymphoid organs with loss of B cell compartments in the spleen, thymus, lymph nodes, and gastrointestinal tract. This results in a severe disruption of B cell function and a hyper-IgM like syndrome. Beyond the pro-B cell stage, B cells are refractory to chemokine stimulation, and splenic B cells are poorly responsive to antigen receptor engagement. Gαi2 and Gαi3 are therefore critical for B cell chemoattractant receptor signaling and for normal B cell function. These mice provide a worst case scenario of the consequences of losing chemoattractant receptor signaling in B cells.

  5. Belimumab: anti-BLyS human monoclonal antibody, anti-BLyS monoclonal antibody, BmAb, human monoclonal antibody to B-lymphocyte stimulator.

    Science.gov (United States)

    2008-01-01

    Belimumab is a fully human monoclonal antibody that specifically recognizes and inhibits the biological activity of B-lymphocyte stimulator, or BLyS. Belimumab is in phase III trials for the treatment of systemic lupus erythematosus (SLE) and has completed a phase II trial in rheumatoid arthritis (RA); the product may also have potential in the treatment of other autoimmune disorders. In May 2001, Cambridge Antibody Technology (now MedImmune) completed its discovery programme and Human Genome Sciences identified belimumab as a candidate for clinical development. More than 1000 distinct human antibodies specific to BLyS were characterized by the collaboration.B-lymphocyte stimulator is a naturally occurring protein discovered by Human Genome Sciences that stimulates B-lymphocytes to develop into mature B cells. Laboratory studies have indicated that higher than normal levels of B-lymphocyte stimulator may contribute to the pathogenesis of autoimmune diseases, such as SLE and RA. Human Genome Sciences (HGS) and Cambridge Antibody Technology signed a collaborative agreement in August 1999 to study the B-lymphocyte stimulator as a human protein target. HGS is also developing other BLyS products. In March 2000, HGS and Cambridge Antibody Technology expanded their agreement into a 10-year collaboration and product development alliance, providing Human Genome Sciences with the right to use the antibody technology of Cambridge Antibody Technology to fully develop human antibodies for therapeutic and diagnostic purposes. Cambridge Antibody Technology will receive royalty payments on product sales from HGS, as well as the development and milestone payments it has already received. Belimumab will be manufactured in Human Genome Sciences' manufacturing facility, located in Rockville, MD, USA. HGS holds commercial rights to the drug. In July 2005, GlaxoSmithKline (GSK) exercised its co-development and co-promotion option to belimumab. In an agreement made in June 1996, HGS had

  6. Deregulation of microRNA expression in purified T and B lymphocytes from patients with primary Sjögren’s syndrome

    Science.gov (United States)

    Wang-Renault, Shu-Fang; Boudaoud, Saida; Nocturne, Gaétane; Roche, Elodie; Sigrist, Nelly; Daviaud, Christian; Bugge Tinggaard, Andreas; Renault, Victor; Deleuze, Jean-François; Mariette, Xavier; Tost, Jörg

    2018-01-01

    Objective MicroRNAs (miRNAs) play an important role in the pathogenesis of autoimmune diseases such as primary Sjögren’s syndrome (pSS). This study is the first to investigate miRNA expression patterns in purified T and B lymphocytes from patients with pSS using a high-throughput quantitative PCR (qPCR) approach. Methods Two independent cohorts of both patients with pSS and controls, one for discovery and one for replication, were included in this study. CD4+ T cells and CD19+ B cells were isolated from peripheral blood mononuclear cells by magnetic microbeads and expression of miRNAs was profiled using the Exiqon Human miRNome panel I analysing 372 miRNAs. A selection of differentially expressed miRNAs was replicated in the second cohort using specific qPCR assays. Results A major difference in miRNA expression patterns was observed between the lymphocyte populations from patients with pSS and controls. In CD4 T lymphocytes, hsa-let-7d-3p, hsa-miR-155–5 p, hsa-miR-222–3 p, hsa-miR-30c-5p, hsa-miR-146a-5p, hsa-miR-378a-3p and hsa-miR-28–5 p were significantly differentially expressed in both the discovery and the replication cohort. In B lymphocytes, hsa-miR-378a-3p, hsa-miR-222–3 p, hsa-miR-26a-5p, hsa-miR-30b-5p and hsa-miR-19b-3p were significantly differentially expressed. Potential target mRNAs were enriched in disease relevant pathways. Expression of B-cell activating factor (BAFF) mRNA was inversely correlated with the expression of hsa-miR-30b-5p in B lymphocytes from patients with pSS and functional experiments showed increased expression of BAFF after inhibiting hsa-miR-30b-5p. Conclusions This study demonstrates major miRNAs deregulation in T and B cells from patients with pSS in two independent cohorts, which might target genes known to be involved in the pathogenesis of pSS. PMID:28916716

  7. Involvement of T- and B-lymphocytes in the immune response to the protein exotoxin and the lipopolysaccharide antigens of Vibrio cholerae

    International Nuclear Information System (INIS)

    Kateley, J.R.; Patel, C.B.; Friedman, H.

    1975-01-01

    The immune response at the level of individual immunocytes to the somatic lipopolysaccharide antigen derived from whole Vibrio cholerae and to the purified protein exotoxin from this organism were studied in terms of the role of T- and B-lymphocytes. By adoptive cell transfer studies with irradiated recipient mice, it was shown that normal spleen cells from normal syngeneic mice could readily transfer the capability of responding to both types of cholera antigens. However, when the spleen cells were depleted of T-cells with anti-theta serum and complement, antibody responsiveness to the LPS antigen, but not the exotoxin, could be achieved in recipients. Furthermore, by appropriate transfer of either bone marrow, thymus, or thymus-marrow cell mixtures to irradiated mice, it was shown that the response to the cholera somatic antigen was relatively independent of thymus cells, whereas the response to exotoxin required ''helper'' T-cells

  8. Early effects of treatment with radium and cobalt-60 gamma radiation on the proportions and absolute counts of T and B lymphocytes in peripheral blood of women with cervical carcinoma

    International Nuclear Information System (INIS)

    Pluzanska, A.; Robak, T.; Kuchowicz, W.; Bartuzel, T.; Studencki, E.; Zadrozna, O.; Mazurowa, A.

    1977-01-01

    In 20 women with cervical carcinoma the T and B lymphocyte counts were determined in peripheral blood. The determinations were carried out before starting treatment and immediately after radium therapy in a mean dose of 6573 mgh and then after full therapeutic dose of cobalt-60 radiation of 4000 R. For identification of T lymphocytes the rosette E test was used and lymphocytes B were identified by means of the EAC rosette test. Presence of immunoglobulins on lymphocytes B was determined as well. In women with cervical carcinoma the total lymphocyte count in 1 mm 3 of blood, the proportions and absolute counts of T and B lymphocytes were not different from those in healthy women. Immediately after radium therapy the lymphocyte count in peripheral blood fell which was due mainly to a fall of the total count and in the proportion of B lymphocytes. The proportion of lymphocytes T was unchanged and their quantitative fall was statistically not significant. After application of the total therapeutic dose of cobalt-60 radiation a further fall of lymphocyte count was observed, due to a fall of the absolute count of T and B lymphocytes. Their proportions were unchanged. (author)

  9. Effect of low doses of ionizing radiation on the thymus-dependent humoral immune response and the polyclonal activation of B-lymphocytes

    International Nuclear Information System (INIS)

    Sharetskij, A.N.; Surinov, B.P.; Abramova, M.R.

    2000-01-01

    The results of studies on the effect of the low-dose (10 cGy with the dose rate of 1cGy/min) γ-radiation on the indices of the mice system and local immune response are presented. The sheep erythrocytes were used as a thymus-dependent antigen. It is shown that the total irradiation with the above dose rate induced the increase in the primary thymus-dependent humoral immune response on the sheep erythrocytes and polyclonal activation of the B-lymphocytes. The sharp oppression of the antibody formation was observed in the immune response dynamics after the phase of the radiation-induced elevation. The injection of hydroquinone right after the irradiation resulted in elimination of the radiation stimulation of the polyclonal response of the B-cells. The essential decrease in the immunoantilogarithmic radiation effect took place in the animals treated with thymogen. The possible negative consequences of the low-dose ionizing radiation impact on the body immune system are discussed [ru

  10. Stage-specific binding profiles of cohesin in resting and activated B lymphocytes suggest a role for cohesin in immunoglobulin class switching and maturation.

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    Gamze Günal-Sadık

    Full Text Available The immunoglobulin heavy chain locus (Igh features higher-order chromosomal interactions to facilitate stage-specific assembly of the Ig molecule. Cohesin, a ring-like protein complex required for sister chromatid cohesion, shapes chromosome architecture and chromatin interactions important for transcriptional regulation and often acts together with CTCF. Cohesin is likely involved in B cell activation and Ig class switch recombination. Hence, binding profiles of cohesin in resting mature murine splenic B lymphocytes and at two stages after cell activation were elucidated by chromatin immunoprecipitation and deep sequencing. Comparative genomic analysis revealed cohesin extensively changes its binding to transcriptional control elements after 48 h of stimulation with LPS/IL-4. Cohesin was clearly underrepresented at switch regions regardless of their activation status, suggesting that switch regions need to be cohesin-poor. Specific binding changes of cohesin at B-cell specific gene loci Pax5 and Blimp-1 indicate new cohesin-dependent regulatory pathways. Together with conserved cohesin/CTCF sites at the Igh 3'RR, a prominent cohesin/CTCF binding site was revealed near the 3' end of Cα where PolII localizes to 3' enhancers. Our study shows that cohesin likely regulates B cell activation and maturation, including Ig class switching.

  11. B Lymphocyte Stimulator (BLyS is expressed in human adipocytes in vivo and is related to obesity but not to insulin resistance.

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    Nike Müller

    Full Text Available Inflammation and metabolism have been shown to be evolutionary linked and increasing evidence exists that pro-inflammatory factors are involved in the pathogenesis of obesity and type 2 diabetes. Until now, most data suggest that within adipose tissue these factors are secreted by cells of the innate immune system, e. g. macrophages. In the present study we demonstrate that B lymphocyte stimulator (BLyS is increased in human obesity. In contrast to several pro-inflammatory factors, we found the source of BLyS in human adipose tissue to be the adipocytes rather than immune cells. In grade 3 obese human subjects, expression of BLyS in vivo in adipose tissue is significantly increased (p<0.001. Furthermore, BLyS serum levels are elevated in grade 3 human obesity (862.5+222.0 pg/ml vs. 543.7+60.7 pg/ml in lean controls, p<0.001 and are positively correlated to the BMI (r = 0.43, p<0.0002. In the present study, bariatric surgery significantly altered serum BLyS concentrations. In contrast, weight loss due to a very-low-calorie-formula-diet (800 kcal/d had no such effect. To examine metabolic activity of BLyS, in a translational research approach, insulin sensitivity was measured in human subjects in vivo before and after treatment with the human recombinant anti-BLyS antibody belimumab. Since BLyS is known to promote B-cell proliferation and immunoglobulin secretion, the present data suggest that adipocytes of grade 3 obese human subjects are able to activate the adaptive immune system, suggesting that in metabolic inflammation in humans both, innate and adaptive immunity, are of pathophysiological relevance.

  12. Induction of DNA and RNA synthesis in murine B lymphocytes does not correlate with early changes in cytosolic free calcium concentration

    International Nuclear Information System (INIS)

    Lebman, D.; Wiener, E.; Scarpa, A.; Cebra, J.

    1986-01-01

    In order to ascertain if early changes in cytosolic free calcium concentration [Ca 2+ ] are correlated with either activation, as defined by 3 H-uridine incorporation or increase in cell size, or induction of DNA synthesis, 3 H-thymidine incorporation, murine B lymphocytes were stimulated with preparations of lipopolysaccharide (LPS), rabbit anti-mouse Fab (RAMFab), and 12-O-tetradecanoyl-phorbol-13-acetate (TPA). LPS, although a potent inducer of 3 H-thymidine incorporation does not cause an increase in [Ca 2+ ]. F(ab') 2 RAMFab at 50 μs ml causes a 6X increase in 3 H-thymidine incorporation as opposed to a 2-3X increase at 10 μg/ml. IgG-RAMFab at concentrations up to 50 μg/ml neither induces DNA synthesis nor activates cells by any criteria, including 3 H-uridine incorporation, increase in cell size, and increase in I-A expression. Both RAMFab causes increases in [Ca 2+ ] that saturate at 10 μg/ml. Minimally proliferative doses of TPA inhibit the increase in [Ca 2+ ] caused by both preparations of RAMFab. However, B cells pretreated with TPA and then stimulated with 2 or 10 μg/ml of either preparation of RAMFab showed increases of 10 X in 3 H-uridine and 100X in 3 H-thymidine incorporation. These data demonstrate that there appears to be no correlation between early changes in [Ca 2+ ] and either activation or induction of DNA synthesis in murine B cells

  13. Trametes versicolor protein YZP activates regulatory B lymphocytes - gene identification through de novo assembly and function analysis in a murine acute colitis model.

    Science.gov (United States)

    Kuan, Yen-Chou; Wu, Ying-Jou; Hung, Chih-Liang; Sheu, Fuu

    2013-01-01

    Trametes versicolor (Yun-Zhi) is a medicinal fungus used as a chemotherapy co-treatment to enhance anti-tumor immunity. Although the efficacies of T. versicolor extracts have been documented, the active ingredients and mechanisms underlying the actions of these extracts remain uncharacterized. We purified a new protein, YZP, from the fruiting bodies of T. versicolor and identified the gene encoding YZP using RNA-seq and de novo assembly technologies. YZP is a 12-kDa non-glycosylated protein comprising 139 amino acids, including an 18-amino acids signal peptide. YZP induced a greater than 60-fold increase in IL-10 secretion in mice B lymphocytes; moreover, YZP specifically triggered the differentiation of CD1d(+) B cells into IL-10-producing regulatory B cells (Bregs) and enhanced the expression of CD1d. YZP-induced B cells suppressed approximately 40% of the LPS-activated macrophage production of inflammatory cytokines in a mixed leukocyte reaction and significantly alleviated the disease activity and colonic inflammation in a DSS-induced acute colitis murine model. Furthermore, YZP activated Breg function via interaction with TLR2 and TLR4 and up-regulation of the TLR-mediated signaling pathway. We purified a novel Breg-stimulating protein, YZP, from T. versicolor and developed an advanced approach combining RNA-seq and de novo assembly technologies.to clone its gene. We demonstrated that YZP activated CD1d(+) Breg differentiation through TLR2/4-mediated signaling pathway, and the YZP-stimulated B cells exhibited anti-inflammatory efficacies in vitro and in murine acute colitis models.

  14. Trametes versicolor protein YZP activates regulatory B lymphocytes - gene identification through de novo assembly and function analysis in a murine acute colitis model.

    Directory of Open Access Journals (Sweden)

    Yen-Chou Kuan

    Full Text Available BACKGROUND: Trametes versicolor (Yun-Zhi is a medicinal fungus used as a chemotherapy co-treatment to enhance anti-tumor immunity. Although the efficacies of T. versicolor extracts have been documented, the active ingredients and mechanisms underlying the actions of these extracts remain uncharacterized. RESULTS: We purified a new protein, YZP, from the fruiting bodies of T. versicolor and identified the gene encoding YZP using RNA-seq and de novo assembly technologies. YZP is a 12-kDa non-glycosylated protein comprising 139 amino acids, including an 18-amino acids signal peptide. YZP induced a greater than 60-fold increase in IL-10 secretion in mice B lymphocytes; moreover, YZP specifically triggered the differentiation of CD1d(+ B cells into IL-10-producing regulatory B cells (Bregs and enhanced the expression of CD1d. YZP-induced B cells suppressed approximately 40% of the LPS-activated macrophage production of inflammatory cytokines in a mixed leukocyte reaction and significantly alleviated the disease activity and colonic inflammation in a DSS-induced acute colitis murine model. Furthermore, YZP activated Breg function via interaction with TLR2 and TLR4 and up-regulation of the TLR-mediated signaling pathway. CONCLUSIONS: We purified a novel Breg-stimulating protein, YZP, from T. versicolor and developed an advanced approach combining RNA-seq and de novo assembly technologies.to clone its gene. We demonstrated that YZP activated CD1d(+ Breg differentiation through TLR2/4-mediated signaling pathway, and the YZP-stimulated B cells exhibited anti-inflammatory efficacies in vitro and in murine acute colitis models.

  15. Trametes versicolor Protein YZP Activates Regulatory B Lymphocytes – Gene Identification through De Novo Assembly and Function Analysis in a Murine Acute Colitis Model

    Science.gov (United States)

    Kuan, Yen-Chou; Wu, Ying-Jou; Hung, Chih-Liang; Sheu, Fuu

    2013-01-01

    Background Trametes versicolor (Yun-Zhi) is a medicinal fungus used as a chemotherapy co-treatment to enhance anti-tumor immunity. Although the efficacies of T. versicolor extracts have been documented, the active ingredients and mechanisms underlying the actions of these extracts remain uncharacterized. Results We purified a new protein, YZP, from the fruiting bodies of T. versicolor and identified the gene encoding YZP using RNA-seq and de novo assembly technologies. YZP is a 12-kDa non-glycosylated protein comprising 139 amino acids, including an 18-amino acids signal peptide. YZP induced a greater than 60-fold increase in IL-10 secretion in mice B lymphocytes; moreover, YZP specifically triggered the differentiation of CD1d+ B cells into IL-10-producing regulatory B cells (Bregs) and enhanced the expression of CD1d. YZP-induced B cells suppressed approximately 40% of the LPS-activated macrophage production of inflammatory cytokines in a mixed leukocyte reaction and significantly alleviated the disease activity and colonic inflammation in a DSS-induced acute colitis murine model. Furthermore, YZP activated Breg function via interaction with TLR2 and TLR4 and up-regulation of the TLR-mediated signaling pathway. Conclusions We purified a novel Breg-stimulating protein, YZP, from T. versicolor and developed an advanced approach combining RNA-seq and de novo assembly technologies.to clone its gene. We demonstrated that YZP activated CD1d+ Breg differentiation through TLR2/4-mediated signaling pathway, and the YZP-stimulated B cells exhibited anti-inflammatory efficacies in vitro and in murine acute colitis models. PMID:24019869

  16. Increased Fas and Bcl-2 Expression on Peripheral Blood T and B Lymphocytes from Juvenile-Onset Systemic Lupus Erythematosus, but not from Juvenile Rheumatoid Arthritis and Juvenile Dermatomyositis

    Directory of Open Access Journals (Sweden)

    Bernadete L. Liphaus

    2006-01-01

    Full Text Available Defective regulation of apoptosis may play a role in the development of autoimmune diseases. Fas and Bcl-2 proteins are involved in the control of apoptosis. The aims of this study were to determine the expression of Fas antigen and Bcl-2 protein on peripheral blood T and B lymphocytes from patients with juvenile-onset systemic lupus erythematosus (JSLE, juvenile rheumatoid arthritis (JRA and juvenile dermatomyositis (JDM. Thirty-eight patients with JSLE, 19 patients with JRA, 10 patients with JDM and 25 healthy controls entered the study. Freshly isolated peripheral blood mononuclear cells (PBMC were stained for lymphocyte markers CD3, CD4, CD8, CD19 and for Fas and Bcl-2 molecules. Expressions were measured by three-color flow cytometry. Statistical analysis was performed using Kruskal–Wallis test. Percentages of freshly isolated T lymphocytes positively stained for Fas protein from JSLE patients were significantly increased compared to healthy controls, patients with JRA and patients with JDM. Percentages of B lymphocytes positive for Fas from JSLE patients were higher than healthy controls and JRA patients. In addition, Fas expression on T cells from patients with JRA was increased compared to JDM patients. Otherwise, Fas expression on T and B cells from JRA and JDM patients were similar to healthy controls. MFI of Bcl-2 positive T lymphocytes from JSLE patients were significantly increased compared to healthy controls and JRA patients. MFI of Bcl-2 protein on B lymphocytes from JSLE patients was similar to healthy controls and patients with JRA and JDM. Bcl-2 expression did not differ between JRA and JDM patients and healthy controls. In conclusion, increased expression of Fas and Bcl-2 proteins observed in circulating T and B lymphocytes from patients with JSLE, but not from patients with JRA and JDM, suggests that abnormalities of apoptosis may be related to the pathogenesis of JSLE and probably are not a result of chronic inflammation.

  17. Benefit from B-lymphocyte depletion using the anti-CD20 antibody rituximab in chronic fatigue syndrome. A double-blind and placebo-controlled study.

    Directory of Open Access Journals (Sweden)

    Øystein Fluge

    Full Text Available Chronic fatigue syndrome (CFS is a disease of unknown aetiology. Major CFS symptom relief during cancer chemotherapy in a patient with synchronous CFS and lymphoma spurred a pilot study of B-lymphocyte depletion using the anti-CD20 antibody Rituximab, which demonstrated significant clinical response in three CFS patients.In this double-blind, placebo-controlled phase II study (NCT00848692, 30 CFS patients were randomised to either Rituximab 500 mg/m(2 or saline, given twice two weeks apart, with follow-up for 12 months. Xenotropic murine leukemia virus-related virus (XMRV was not detected in any of the patients. The responses generally affected all CFS symptoms. Major or moderate overall response, defined as lasting improvements in self-reported Fatigue score during follow-up, was seen in 10 out of 15 patients (67% in the Rituximab group and in two out of 15 patients (13% in the Placebo group (p = 0.003. Mean response duration within the follow-up period for the 10 responders to Rituximab was 25 weeks (range 8-44. Four Rituximab patients had clinical response durations past the study period. General linear models for repeated measures of Fatigue scores during follow-up showed a significant interaction between time and intervention group (p = 0.018 for self-reported, and p = 0.024 for physician-assessed, with differences between the Rituximab and Placebo groups between 6-10 months after intervention. The primary end-point, defined as effect on self-reported Fatigue score 3 months after intervention, was negative. There were no serious adverse events. Two patients in the Rituximab group with pre-existing psoriasis experienced moderate psoriasis worsening.The delayed responses starting from 2-7 months after Rituximab treatment, in spite of rapid B-cell depletion, suggests that CFS is an autoimmune disease and may be consistent with the gradual elimination of autoantibodies preceding clinical responses. The present findings will impact

  18. Genetic evidence for single-strand lesions initiating Nbs1-dependent homologous recombination in diversification of Ig v in chicken B lymphocytes.

    Directory of Open Access Journals (Sweden)

    Makoto Nakahara

    2009-01-01

    Full Text Available Homologous recombination (HR is initiated by DNA double-strand breaks (DSB. However, it remains unclear whether single-strand lesions also initiate HR in genomic DNA. Chicken B lymphocytes diversify their Immunoglobulin (Ig V genes through HR (Ig gene conversion and non-templated hypermutation. Both types of Ig V diversification are initiated by AID-dependent abasic-site formation. Abasic sites stall replication, resulting in the formation of single-stranded gaps. These gaps can be filled by error-prone DNA polymerases, resulting in hypermutation. However, it is unclear whether these single-strand gaps can also initiate Ig gene conversion without being first converted to DSBs. The Mre11-Rad50-Nbs1 (MRN complex, which produces 3' single-strand overhangs, promotes the initiation of DSB-induced HR in yeast. We show that a DT40 line expressing only a truncated form of Nbs1 (Nbs1(p70 exhibits defective HR-dependent DSB repair, and a significant reduction in the rate--though not the fidelity--of Ig gene conversion. Interestingly, this defective gene conversion was restored to wild type levels by overproduction of Escherichia coli SbcB, a 3' to 5' single-strand-specific exonuclease, without affecting DSB repair. Conversely, overexpression of chicken Exo1 increased the efficiency of DSB-induced gene-targeting more than 10-fold, with no effect on Ig gene conversion. These results suggest that Ig gene conversion may be initiated by single-strand gaps rather than by DSBs, and, like SbcB, the MRN complex in DT40 may convert AID-induced lesions into single-strand gaps suitable for triggering HR. In summary, Ig gene conversion and hypermutation may share a common substrate-single-stranded gaps. Genetic analysis of the two types of Ig V diversification in DT40 provides a unique opportunity to gain insight into the molecular mechanisms underlying the filling of gaps that arise as a consequence of replication blocks at abasic sites, by HR and error

  19. Complement receptors type 1 (CR1, CD35) and 2 (CR2, CD21) cooperate in the binding of hydrolyzed complement factor 3 (C3i) to human B lymphocytes

    DEFF Research Database (Denmark)

    Leslie, Robert Graham Quinton; Prodinger, Wolfgang Maria; Nielsen, Claus Henrik

    2003-01-01

    and CR2, operating independently, differed ca. 9-fold (k(1)=193+/-9.4 and 22.2+/-6.0 x 10(3) M(-1)s(-1), respectively). Equilibrium binding of C3i to B lymphocytes was also complex, varying in strength by ca. 13-fold over the C3i concentration range examined. The maximum association constant (K(a, max......)=109+/-27.2 x 10(7) l/mole) was ca. 9- and 6-fold greater, respectively, than those for CR1 or CR2 acting alone (K(a)=13.2+/-5.3 and 18.5+/-3.5 x 10(7) l/mole). The high avidity of the CR1-CR2 complex for C3i is consistent with its rates of C3i uptake and release being determined by CR1 and CR2...

  20. Absence of CD4+ T lymphocytes, CD8+ T lymphocytes, or B lymphocytes has different effects on the efficacy of posaconazole and benznidazole in treatment of experimental acute Trypanosoma cruzi infection.

    Science.gov (United States)

    Ferraz, Marcela L; Gazzinelli, Ricardo T; Alves, Rosana O; Urbina, Julio A; Romanha, Alvaro J

    2009-01-01

    We investigated the influence of CD4(+) T lymphocytes, CD8(+) T lymphocytes, and B lymphocytes on the efficacy of posaconazole (POS) and the reference drug benznidazole (BZ) during treatment of acute Trypanosoma cruzi infection in a murine model. Wild-type mice infected with T. cruzi and treated with POS or BZ presented no parasitemia, 100% survival, and 86 to 89% cure rates, defined as the percentages of animals with negative hemocultures at the end of the observation period. CD4(+)-T-lymphocyte-knockout (KO) mice infected with T. cruzi and treated with BZ or POS controlled parasitemia during treatment, although circulating parasites reappeared after drug pressure cessation, leading to only a 6% survival rate and no cure. CD8(+)-T-lymphocyte-KO mice infected with T. cruzi and treated with POS or BZ had intermediate results, displaying discrete parasitemia after the treatment was ended, 81 and 86% survival, and cure rates of 31 and 66%, respectively. B-lymphocyte-KO mice infected with T. cruzi and treated with BZ relapsed with parasitemia 1 week after the end of treatment and had a 67% survival rate and only a 22% cure rate. In contrast, the activity of POS was much less affected in these animals, with permanent suppression of parasitemia, 100% survival, and a 71% cure rate. Our results demonstrate that abrogation of different lymphocytes' activities has distinct effects on the efficacy of POS and BZ in this experimental model, probably reflecting different parasite stages preferentially targeted by the two drugs and distinct cooperation patterns with the host immune system.

  1. Analysis of globotriaosylceramide (Gb3) isoforms/analogs in unfractionated leukocytes, B lymphocytes and monocytes from Fabry patients using ultra-high performance liquid chromatography/tandem mass spectrometry.

    Science.gov (United States)

    Toupin, Amanda; Lavoie, Pamela; Arthus, Marie-Françoise; Abaoui, Mona; Boutin, Michel; Fortier, Carole; Ménard, Claudia; Bichet, Daniel G; Auray-Blais, Christiane

    2018-07-26

    Fabry disease is an X-linked lysosomal storage disorder with marked variability in the phenotype and genotype. Glycosphingolipids such as globotriaosylceramide (Gb 3 ) isoforms/analogs, globotriaosylsphingosine (lyso-Gb 3 ) and analogs, and galabiosylceramide (Ga 2 ) isoforms/analogs may accumulate in biological fluids and different organs. The aims of this study were to: 1) develop/validate a novel UHPLC-MS/MS method for relative quantitation of Gb 3 in leukocytes (unfractionated white blood cells), B lymphocytes and monocytes; 2) evaluate these biomarkers in a cohort of Fabry patients and healthy controls; and 3) assess correlations between these biomarkers, treatment and genotype. Whole blood, plasma and urine samples from 21 Fabry patients and 20 healthy controls were analyzed. Samples were purified by liquid-liquid extraction and analyzed by UHPLC-MS/MS in positive electrospray ionization. Methylated Gb 3 isoforms were detected, showing that a methylation process occurs at the cellular level. Our results show that there were no significant differences in the distribution of the different Gb 3 isoforms/analogs in blood cells between Fabry patients and healthy controls. In leukocyte, Gb 3 [(d18:1)(C14:0)], Gb 3 [(d18:1)(C16:0)], Gb 3 [(d18:1)(C16:0)]Me, Gb 3 [(d18:1)(C16:1)], Gb 3 [(d18:1)(C18:0)], Gb 3 [(d18:1)(C18:1)], Gb 3 [(d18:1)(C20:1)], Gb 3 [(d18:1)(C24:2)], Gb 3 [(d18:1)(C26:1)] and total Gb 3 allowed good discrimination between male Fabry patients and male controls, patients having higher biomarker levels than controls. Regarding B lymphocytes and monocytes, the same tendency was observed without reaching statistical significance. A positive concordance between mutation types and biomarker levels in white blood cells was established. Our results might provide a deeper mechanistic comprehension of the underlying biochemical processes of Gb 3 biomarkers in white blood cells of Fabry patients. Copyright © 2018 Elsevier B.V. All rights reserved.

  2. Equine Arteritis Virus Has Specific Tropism for Stromal Cells and CD8+T and CD21+B Lymphocytes but Not for Glandular Epithelium at the Primary Site of Persistent Infection in the Stallion Reproductive Tract.

    Science.gov (United States)

    Carossino, Mariano; Loynachan, Alan T; Canisso, Igor F; Cook, R Frank; Campos, Juliana R; Nam, Bora; Go, Yun Young; Squires, Edward L; Troedsson, Mats H T; Swerczek, Thomas; Del Piero, Fabio; Bailey, Ernest; Timoney, Peter J; Balasuriya, Udeni B R

    2017-07-01

    Equine arteritis virus (EAV) has a global impact on the equine industry as the causative agent of equine viral arteritis (EVA), a respiratory, systemic, and reproductive disease of equids. A distinctive feature of EAV infection is that it establishes long-term persistent infection in 10 to 70% of infected stallions (carriers). In these stallions, EAV is detectable only in the reproductive tract, and viral persistence occurs despite the presence of high serum neutralizing antibody titers. Carrier stallions constitute the natural reservoir of the virus as they continuously shed EAV in their semen. Although the accessory sex glands have been implicated as the primary sites of EAV persistence, the viral host cell tropism and whether viral replication in carrier stallions occurs in the presence or absence of host inflammatory responses remain unknown. In this study, dual immunohistochemical and immunofluorescence techniques were employed to unequivocally demonstrate that the ampulla is the main EAV tissue reservoir rather than immunologically privileged tissues (i.e., testes). Furthermore, we demonstrate that EAV has specific tropism for stromal cells (fibrocytes and possibly tissue macrophages) and CD8 + T and CD21 + B lymphocytes but not glandular epithelium. Persistent EAV infection is associated with moderate, multifocal lymphoplasmacytic ampullitis comprising clusters of B (CD21 + ) lymphocytes and significant infiltration of T (CD3 + , CD4 + , CD8 + , and CD25 + ) lymphocytes, tissue macrophages, and dendritic cells (Iba-1 + and CD83 + ), with a small number of tissue macrophages expressing CD163 and CD204 scavenger receptors. This study suggests that EAV employs complex immune evasion mechanisms that warrant further investigation. IMPORTANCE The major challenge for the worldwide control of EAV is that this virus has the distinctive ability to establish persistent infection in the stallion's reproductive tract as a mechanism to ensure its maintenance in equid

  3. Live vaccinia-rabies virus recombinants, but not an inactivated rabies virus cell culture vaccine, protect B-lymphocyte-deficient A/WySnJ mice against rabies: considerations of recombinant defective poxviruses for rabies immunization of immunocompromised individuals.

    Science.gov (United States)

    Lodmell, Donald L; Esposito, Joseph J; Ewalt, Larry C

    2004-09-03

    Presently, commercially available cell culture rabies vaccines for humans and animals consist of the five inactivated rabies virus proteins. The vaccines elicit a CD4+ helper T-cell response and a humoral B-cell response against the viral glycoprotein (G) resulting in the production of virus neutralizing antibody. Antibody against the viral nucleoprotein (N) is also present, but the mechanism(s) of its protection is unclear. HIV-infected individuals with low CD4+ T-lymphocyte counts and individuals undergoing treatment with immunosuppressive drugs have an impaired neutralizing antibody response after pre- and post-exposure immunization with rabies cell culture vaccines. Here we show the efficacy of live vaccinia-rabies virus recombinants, but not a cell culture vaccine consisting of inactivated rabies virus, to elicit elevated levels of neutralizing antibody in B-lymphocyte deficient A/WySnJ mice. The cell culture vaccine also failed to protect the mice, whereas a single immunization of a vaccinia recombinant expressing the rabies virus G or co-expressing G and N equally protected the mice up to 18 months after vaccination. The data suggest that recombinant poxviruses expressing the rabies virus G, in particular replication defective poxviruses such as canarypox or MVA vaccinia virus that undergo abortive replication in non-avian cells, or the attenuated vaccinia virus NYVAC, should be evaluated as rabies vaccines in immunocompromised individuals.

  4. Imaging B lymphocytes in autoimmune inflammatory diseases

    International Nuclear Information System (INIS)

    Iodice, V.; Lauri, C.; Capriotti, G.; Lagana', B.; Germano, V.; D’Amelio, R.; Picchianti Diamanti, A.

    2014-01-01

    B cells arise from stem cells precursor and develop through a tightly regulated and selective process that lead to the generation of different B cell populations such as transitional, mature, memory and plasma cells. These B cell subsets can be identified using flow cytometry by the expression of specific surface antigens. The growing knowledge of the pivotal role played by B cells in the development and progression of autoimmune diseases combined with the advances in monoclonal antibody technology, led in the last years to the generation of different biological agents targeting B cells. In this context, nuclear medicine can offer the possibility to use a panel of biologic radiopharmaceuticals for molecular imaging of inflammatory diseases. Radiopharmaceuticals bind to their targets with high affinity and specificity and have an excellent imaging diagnostic potential for the evaluation of disease activity, selection and monitoring of immune therapies. Several molecules have been radiolabelled for the imaging of T lymphocytes whereas, by now, the anti CD20 rituximab is the only biological therapy targeting B cells that demonstrated to be efficiently radiolabelled and used to detect inflammation in autoimmune patients

  5. B lymphocyte differentiation in the mouse

    NARCIS (Netherlands)

    J. Rozing (Jan)

    1977-01-01

    textabstractWhen an antigen enters the body, it can react upon such an invasion with a nonspecific and a specific defense mechardsm. Phagocytic white blood cells can attack antigens, such as present on the surface of bacteria and viruses, non-specifically by engulfing and destroying these particles.

  6. Effects of heat stress on peripheral T and B lymphocyte profiles and IgG and IgM serum levels in broiler chickens vaccinated for Newcastle disease virus.

    Science.gov (United States)

    Honda, Bruno Takashi Bueno; Calefi, Atilio Sersun; Costola-de-Souza, Carolina; Quinteiro-Filho, Wanderley Moreno; da Silva Fonseca, Juliana Garcia; de Paula, Viviane Ferraz; Palermo-Neto, João

    2015-10-01

    Multiple factors, such as environment, nutritional status, and disease, induce stress in animals during livestock production. It has been shown that poultry exposed to stressors for prolonged periods had decreases in their performance parameters, mortality and decreased host resistance to pathogenic agents. It seems that early age stress may have long-lasting impact and could possibly modify the expression of their genetic potential on growth performance and immunity. This study aimed to discuss the effects of early-age heat stress on the blood lymphocyte phenotypes (B and T lymphocytes) and plasma immunoglobulin levels (IgM and IgG) in chickens vaccinated against paramixovirus of the Newcastle (NC) disease (LaSota strain). For this purpose, 96 male chickens (Cobb) were divided into 4 groups: 1) control (C), 2) heat-stressed (HS), 3) control vaccinated (C/V), and 4) heat-stressed and Vaccinated (HS/V). The NC vaccine was administered twice on experimental day (ED) 7 and ED14, and the heat stress (38 ± 1°C) was applied from ED2 to ED6. The data showed that HS increased the corticosterone serum levels in the HS group compared with the control groups (C and C/V groups). At ED7, increased concentrations of IgM were observed in birds in the HS and HS/V groups compared with C and C/V animals; chickens from the HS/V group presented increased IgG levels compared with those in the birds of the C group. The heat stress shifted the immune cell profile from B-lymphocyte to a T-cytotoxic and T-helper lymphocyte profile, and this immune cell pattern persisted until the end of the study period. It was concluded that heat stress immunomodulated the immune function response of the chickens to the NC disease vaccine challenge. © 2015 Poultry Science Association Inc.

  7. Classical and alternative activation and metalloproteinase expression occurs in foam cell macrophages in male and female ApoE null mice in the absence of T- and B-lymphocytes

    Directory of Open Access Journals (Sweden)

    Elaine Mo Hayes

    2014-10-01

    Full Text Available Background: Rupture of advanced atherosclerotic plaques accounts for most life-threatening myocardial infarctions. Classical (M1 and alternative (M2 macrophage activation could promote atherosclerotic plaque progression and rupture by increasing production of proteases, including matrix metalloproteinases (MMPs. Lymphocyte-derived cytokines may be essential for generating M1 and M2 phenotypes in plaques, although this has not been rigorously tested until now.Methods and Results: We validated the expression of M1 markers (iNOS and COX-2 and M2 markers (arginase-1, Ym-1 and CD206 and then measured MMP mRNA levels in mouse macrophages during classical and alternative activation in vitro. We then compared mRNA expression of these genes ex vivo in foam cells from subcutaneous granulomas in fat-fed immune-competent ApoE knockout and immune-compromised ApoE/Rag-1 double knockout mice, which lack all T and B cells. Furthermore, we performed immunohistochemistry in subcutaneous granulomas and in aortic root and brachiocephalic artery atherosclerotic plaques to measure the extent of M1/M2 marker and MMP protein expression in vivo. Classical activation of mouse macrophages with bacterial lipopolysaccharide in vitro increased MMPs-13, -14 and -25 but decreased MMP-19 and TIMP-2 mRNA expressions. Alternative activation with IL-4 increased MMP-19 expression. Foam cells in subcutaneous granulomas expressed all M1/M2 markers and MMPs at ex vivo mRNA and in vivo protein levels, irrespective of Rag-1 genotype. There were also similar percentages of foam cell macrophages carrying M1/M2 markers and MMPs in atherosclerotic plaques from ApoE knockout and ApoE/Rag-1 double knockout mice. Conclusions: Classical and alternative activation leads to distinct MMP expression patterns in mouse macrophages in vitro. M1 and M2 polarization in vivo occurs in the absence of T and B lymphocytes in either granuloma or plaque foam cell macrophages.

  8. Genesis of B lymphocytes in the bone marrow: extravascular and intravascular localization of surface IgM-bearing cells in mouse bone marrow detected by electron-microscope radioautography after in vivo perfusion of 125I anti-IgM antibody

    International Nuclear Information System (INIS)

    Osmond, D.G.; Batten, S.J.

    1984-01-01

    The role of mammalian bone marrow in generating surface IgM (sIgM)-bearing B lymphocytes is reviewed. Precursor cells in the marrow give rise to large, rapidly dividing cells bearing free cytoplasmic mu chains (c mu). The progeny of the large c mu+ cells form a population of small, nondividing c mu+ cells that mature into small lymphocytes, progressively expressing sIgM and other B-cell surface membrane components. Newly formed sIgM+ cells soon migrate through the bloodstream to the spleen and other lymphoid tissues, where they may die after a short lifespan or be activated to produce antibody molecules. The large-scale lymphocytopoiesis in the bone marrow thus maintains a population of rapidly renewed virgin B lymphocytes in the peripheral lymphoid tissues. A technique for perfusing radiolabeled anti-IgM antibodies in young mice has now permitted sIgM+ cells to be detected radioautographically in histological preparations of bone marrow under the electron microscope. Small sIgM+ lymphocytes are situated either singly or in small groups throughout the extravascular hemopoietic compartment of the bone marrow, often near sinusoid walls adjacent to late erythroblasts and reticular cells. Some regional concentrations of sIgM+ cells are apparent. sIgM+ cells also appear in transit through the sinusoidal endothelium and are markedly concentrated in the lumen of some sinusoids. Intrasinusoidal sIgM+ small lymphocytes have high densities of sIgM and long microvilli, on which sIgM molecules are concentrated. These studies reveal the localization and cell associations of specifically identified sIgM+ small lymphocytes in the extravascular marrow compartment and suggest that these cells may also undergo a transient intravascular storage and maturation phase. Use of this in vivo immunolabeling technique to detect other cell-surface markers may further elucidate the microenvironmental basis of B lymphocyte genesis in the bone marrow

  9. Altered B lymphocyte homeostasis and functions in systemic sclerosis.

    Science.gov (United States)

    Forestier, Alexandra; Guerrier, Thomas; Jouvray, Mathieu; Giovannelli, Jonathan; Lefèvre, Guillaume; Sobanski, Vincent; Hauspie, Carine; Hachulla, Eric; Hatron, Pierre-Yves; Zéphir, Hélène; Vermersch, Patrick; Labalette, Myriam; Launay, David; Dubucquoi, Sylvain

    2018-03-01

    Beyond the production of autoantibodies, B-cells are thought to play a role in systemic sclerosis (SSc) by secreting proinflammatory/profibrotic cytokines. B-cells are a heterogeneous population with different subsets distinguished by their phenotypes and cytokine production. Data about B-cell subsets, cytokine production and intracellular pathways leading to this production are scarce in SSc. The aim of our study was to describe B-cell homeostasis, activation, proliferation, cytokine production in B-cells and serum and B-cell intracellular signaling pathways in SSc. We hypothezided that B-cell homeostasis and cytokine production were altered in SSc and could be explained by serum cytokine as well as by intracellular signaling pathway abnormalities. Forty SSc patients and 20 healthy controls (HC) were prospectively included. B-cell subsets were determined by flow cytometry using CD19, CD21, CD24, CD38, CD27, IgM and IgD. CD25, CD80, CD95, HLA-DR were used to assess B-cell activation. Intracellular production of IL-10 and IL-6 were assessed by flow cytometry after TLR9 and CD40 stimulation. IL-6, IL-10, Ki67, Bcl2 mRNA were quantified in B-cells. Cytokine production was also assessed in sera and supernatants of B-cell culture, using a multiplex approach. Signaling pathways were studied through phosphorylation of mTOR, ERK, STAT3, STAT5 using a flow cytometry approach. We found that SSc patients exhibited an altered peripheral blood B-cell subset distribution, with decreased memory B-cells but increased proportion of naive and CD21 Lo CD38 Lo B-cell subsets. We observed an increased expression of activation markers (CD80, CD95, HLA-DR) on some B-cell subsets, mainly the memory B-cells. Secretion of IL-6, BAFF and CXCL13 were increased in SSc sera. There was no correlation between the peripheral blood B-cell subsets and the serum concentrations of these cytokines. After stimulation, we observed a lower proportion of IL-10 and IL-6 producing B-cells in SSc. Finally, we observed a significant decrease of mTOR phosphorylation in SSc patient B-cells. In conclusion, we observed an altered B-cell homeostasis in SSc patients compared to HC. Memory B-cells were both decreased and activated in patients. IL-10 producing B-cells were decreased in SSc. This decrease was associated with an alteration of mTOR phosphorylation in B-cells. Conversely, there was no correlation between serum cytokine profile and B-cell homeostasis alterations. Copyright © 2018 Elsevier B.V. All rights reserved.

  10. B lymphocyte lineage cells and the respiratory system

    Science.gov (United States)

    Kato, Atsushi; Hulse, Kathryn E.; Tan, Bruce K.; Schleimer, Robert P.

    2013-01-01

    Adaptive humoral immune responses in the airways are mediated by B cells and plasma cells that express highly evolved and specific receptors and produce immunoglobulins of most isotypes. In some cases, such as autoimmune diseases or inflammatory diseases caused by excessive exposure to foreign antigens, these same immune cells can cause disease by virtue of overly vigorous responses. This review discusses the generation, differentiation, signaling, activation and recruitment pathways of B cells and plasma cells, with special emphasis on unique characteristics of subsets of these cells functioning within the respiratory system. The primary sensitization events that generate B cells responsible for effector responses throughout the airways usually occur in the upper airways, in tonsils and adenoid structures that make up Waldeyer’s Ring. Upon secondary exposure to antigen in the airways, antigen-processing dendritic cells migrate into secondary lymphoid organs such as lymph nodes that drain the upper and lower airways and further B cell expansion takes place at those sites. Antigen exposure in the upper or lower airways can also drive expansion of B lineage cells in the airway mucosal tissue and lead to the formation of inducible lymphoid follicles or aggregates that can mediate local immunity or disease. PMID:23540615

  11. CD45 (leucocyte common antigen) expression in T and B lymphocyte subsets

    NARCIS (Netherlands)

    Poppema, S; Lai, R; Visser, L; Yan, X J

    CD45 is the dominant tyrosine phosphatase in haematopoietic cells and can modulate the effects of many other signaling molecules by dephosphorylation. The extracellular portion of CD45 has considerable variability due to differential splicing and glycosylation. This may allow for interactions with a

  12. RhoA of the Rho family small GTPases is essential for B lymphocyte development.

    Directory of Open Access Journals (Sweden)

    Shuangmin Zhang

    Full Text Available RhoA is a member of the Rho family small GTPases that are implicated in various cell functions including proliferation and survival. However, the physiological role of RhoA in vivo remains largely unknown. Here, we deleted RhoA in the B cell and hematopoietic stem cell (HSC populations in RhoA(flox/flox mice with CD19 and Mx promoter-driven Cre expression, respectively. Deletion of RhoA by CD19(Cre/+ significantly blocked B cell development in spleen, leading to a marked reduction in the number of transitional, marginal zone, and follicular B cells. Surprisingly, neither B cell proliferation in response to either LPS or B cell receptor (BCR engagement nor B cell survival rate in vivo was affected by RhoA deletion. Furthermore, RhoA(-/- B cells, like control cells, were rescued from apoptosis by BCR crosslinking in vitro. In contrast, RhoA deficiency led to a defect in B cell activating factor (BAFF-mediated B cell survival that was associated with a dampened expression of BAFF receptor and a loss of BAFF-mediated Akt activation. Finally, HSC deletion of RhoA by Mx-Cre severely reduced proB/preB and immature B cell populations in bone marrow while common lymphoid progenitors were increased, indicating that RhoA is also required for B cell progenitor/precursor differentiation. Taken together, our results uncover an important role for RhoA at multiple stages of B cell development.

  13. Functional implications of B lymphocytes in the development of rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Juan-Manuel Anaya

    2006-04-01

    Full Text Available B cells play a key role in regulating the immune system by producingantibodies, acting as antigen-presenting cells, providing support toother mononuclear cells, and contributing directly to inflammatorypathways. Accumulating evidence indicates that there is a disruptionof these regulated processes in the pathogenesis of autoimmunediseases, including rheumatoid arthritis (RA. In RA there is a chronic inflammation in the affected joints leading to the development of ectopic germinal centers. A micro-environment is established which supports B cell activation and differentiation. Plasma cells may develop which secrete autoantibodies of high affinity directly into the synovial tissue. As a result, antigen/antibody complex formation, the activation of the complement cascade and the stimulation of macrophages may contribute to the destruction of joints. B cells also play a pivotal role in the activation of synovial T cells and the induction of cytokine secretion. Finally, the success of B cell depletion therapy by using monoclonal antibodies against CD20 further emphasized the importance of B cells in the pathogenesis of RA

  14. Prospective neonatal screening for severe T- and B-lymphocyte deficiencies in Seville.

    Science.gov (United States)

    de Felipe, Beatriz; Olbrich, Peter; Lucenas, José Manuel; Delgado-Pecellin, Carmen; Pavon-Delgado, Antonio; Marquez, Josefina; Salamanca, Carmen; Soler-Palacin, Pere; Gonzalez-Granado, Luis Ignacio; Antolin, Laura Ferreras; Borte, Stephan; Neth, Olaf

    2016-02-01

    Early diagnosis of primary immunodeficiency such as severe combined immunodeficiency (SCID) and X-linked agammaglobulinemia (XLA) improves outcome of affected children. T-cell-receptor-excision circles (TRECs) and kappa-deleting-recombination-excision circles (KRECs) determination from dried blood spots (DBS) identify neonates with severe T- and/or B-lymphopenia. No prospective data exist of the impact of gestational age (GA) and birth weight (BW) on TRECs and KRECs values. TRECs and KRECs determination using triplex RT-PCR (TRECS-KRECS-β-actin-Assay) from prospectively collected DBS between 02/2014 and 02/2015 in three hospitals in Seville, Spain. Cut-off levels were TRECs 700/punch. Internal (SCID, XLA, ataxia telangiectasia) and external controls (NBS quality assurance program, CDC) were included. A total of 5160 DBS were tested. Re-punch was needed in 77 samples (1.5%) due to insufficient β-actin (<700 copies/punch). Pre-term neonates (GA<37 weeks) and neonates with a BW<2500 g showed significantly lower TRECs and KRECs levels (p < 0.001). Due to repeat positive results five neonates were re-called (<0.1%): Fatal chromosomopathy (n = 1; TRECs 1/KRECs 4); extreme pre-maturity (n = 2; TRECs 0/KRECs 0 and TRECs 1/KRECs 20 copies/punch); neonates born to mothers receiving azathioprine during pregnancy (n = 2; TRECs 92/KRECs 1 and TRECs 154/KRECs 3 copies/punch). All internal and external controls were correctly identified. TRECS-KRECS-β-actin-Assay correctly identifies T- and B-cell lymphopenias. Pre-maturity and low BW is associated with lower TREC and KREC levels. Extreme pre-maturity and maternal immune suppressive therapy may be a cause for false positive results of TRECs and KRECs values, respectively. To reduce the rate of insufficient samples, DBS extraction and storage need to be improved. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. B Lymphocyte Subpopulation Defined by a Rat Monoclonal Antibody, 14G8

    Science.gov (United States)

    1982-05-01

    ability to bind to DBA/,Supprted I pert by tie Naval Medical Research and Deveopment CO 2 p~e cells. The screening procedure Involved the reaction of...followed by XRITC-avldin. They were then subjected to dualmenu. fluorescence. FMF analysis as described In Maltials and Metods . Arrows 14G8 reacts...cPu vedkw" nl AnUsp A CPM CPM 168 351 163 658 N.D. - 531 944 413 Una , 1.751 18.796 16.045 3.445 15,259 11.814 1.981 23.434 21.453 1406 bright 7.579

  16. Corruption of human follicular B-lymphocyte trafficking by a B-cell superantigen.

    Science.gov (United States)

    Borhis, Gwenoline; Viau, Muriel; Badr, Gamal; Richard, Yolande; Zouali, Moncef

    2012-05-09

    Protein A (SpA) of Staphylococcus aureus is known to target the paratope of immunoglobulins expressing V(H)3 genes, and to delete marginal zone B cells and B-1a in vivo. We have discovered that SpA endows S. aureus with the potential to subvert B-cell trafficking in the host. We found that SpA, whose Fc-binding site has been inactivated, binds essentially to naïve B cells and induces a long-lasting decrease in CXCR4 expression and in B-cell chemotaxis to CXCL12. Competition experiments indicated that SpA does not interfere with binding of CXCR4 ligands and does not directly bind to CXCR4. This conclusion is strongly supported by the inability of SpA to modulate clathrin-mediated CXCR4 internalization, which contrasts with the potent effect of anti-immunoglobin M (IgM) antibodies. Microscopy and biochemical experiments confirmed that SpA binds to the surface IgM/IgD complex and induces its clathrin-dependent internalization. Concomitantly, the SpA-induced signaling leads to protein kinase C-dependent CXCR4 downmodulation, suggesting that SpA impairs the recycling of CXCR4, a postclathrin process that leads to either degradation into lysozomes or de novo expression at the cell surface. In addition to providing novel insight into disruption of B-cell trafficking by an infectious agent, our findings may have therapeutic implications. Because CXCR4 has been associated with cancer metastasis and with certain autoimmune diseases, SpA behaves as an evolutionary tailored highly specific, chemokine receptor inhibitor that may have value in addition to conventional cytotoxic therapy in patients with various malignancies and immune-mediated diseases.

  17. Radiosensitivity of T and B lymphocytes. III. Effect of radiation on immunoglobulin production by B cells

    International Nuclear Information System (INIS)

    Anderson, R.E.; Warner, N.L.

    1975-01-01

    Radiation injury in defined populations of B cells was investigated utilizing an allotype congenic transfer system. The amount of donor immunoglobulin present in the recipient's serum was found to be directly proportional to the number of viable cells injected, and on this basis approximate D 37 values for the inoculated B cells were determined in several experiments and found to fall in the 70 to 145 rad range depending upon the specific experimental conditions. Since the sensitivity of T cells to radiation-induced interphase death can be modified by prior exposure to select mitogens and antigens, an attempt was made to demonstrate a similar phenomenon with respect to B cells. The results indicate that the radiosensitivity of B cells can be slightly influenced by prior incubation with mitogens and only equivocally changed by activation with antigen. (U.S.)

  18. Role of the spleen in the maturation of B-lymphocytes

    International Nuclear Information System (INIS)

    Strober, S.

    1976-01-01

    Spleen cells from unimmunized Lewis rats were fractionated by 1 x g velocity sedimentation and assayed for their ability to restore the adoptive primary antibody response to horse spleen ferritin in irradiated syngeneic recipients given T cell supplementation. Large, medium and small cell fractions all showed virgin B cell activity. Similar studies with thoractic duct cells show that virgin B cell activity is restricted to the small and medium cells. Large spleen cells produced a 2-ME sensitive adoptive antibody response which persisted for 21 days. All antibody produced by small cells at 21 days was 2-ME resistant. Examination of spleen cells during recovery from sublethal irradiation showed that virgin B cell activity was first detected at 14 days, and is confined to the large cell fraction. Experiments with congenic rats which differ at the immunoglobulin (Ig) light chain allotype showed that small cells from the bone marrow injected intravenously can transform into large Ig-bearing cells in the spleen. The relationship of the subclasses of virgin B cells in the spleen to B cell maturation is discussed

  19. Signal thresholds and modular synergy during expression of costimulatory molecules in B lymphocytes.

    Science.gov (United States)

    Natarajan, K; Sahoo, N C; Rao, K V

    2001-07-01

    We analyzed intracellular pathways modulating surface densities of CD80 and CD86 in B cells activated through ligation of the Ag receptor, and the adhesion molecule CD54. Whereas B cell Ag receptor (BCR) cross-linking alone stimulated increased expression of CD86, up-regulation of CD80 required dual stimulation with anti-IgM and anti-CD54. The principal downstream component contributed by BCR signaling, toward both CD80 and CD86 induction, was the elevated concentration of free cytoplasmic Ca(2+), recruited by way of capacitative influx. This alone was sufficient to generate an increase in CD86 levels. However, CD80 enhancement required the concerted action of both intracellular Ca(2+) concentration and CD54-initiated pathways. The nexus between anti-IgM and anti-CD54 stimulation, in the context of CD80 regulation, was identified to involve a self-propagating process of sequential synergy. The first step involved amplified accumulation of intracellular cAMP, as a result of cross-talk between BCR-mobilized Ca(2+) and CD54-derived signals. This then facilitated a second synergistic interaction between Ca(2+) and cAMP, culminating in CD80 expression. Our findings of distinct signal transducer requirements, with the added consequences of cross-talk, offers an explanation for variable modulation of costimulatory molecule expression in response to diverse physiological stimuli. Importantly, these results also reveal how concentration threshold barriers for recruitment of individual second messengers can be overcome by constructive convergence of signaling modules.

  20. Regulation of Mitochondria Function by TRAF3 in B Lymphocytes and B Cell Malignancies

    Science.gov (United States)

    2015-10-01

    membrane potential, respiration and energy production, reactive oxygen species production, mitochondria phospholipid levels, and mitochondrial gene...reactive oxygen species (ROS) production and adenine nucleotides: Mitochondrial dysfunction may lead to increased ROS production and consequently oxidative...and Inhibits Inflammation and Tumor Development in Mice. Abstract #: Z4 3027. Keystone Symposia: Mechanisms of Pro-Inflammatory Diseases, Olympic

  1. Distinct nuclear orientation patterns for mouse chromosome 11 in normal B lymphocytes

    NARCIS (Netherlands)

    Schmälter, A.K.; Kuzyk, A.; Righolt, C.H.; Neusser, M.; Steinlein, O.K.; Müller, S.; Mai, S.

    2014-01-01

    Background Characterizing the nuclear orientation of chromosomes in the three-dimensional (3D) nucleus by multicolor banding (mBANDing) is a new approach towards understanding nuclear organization of chromosome territories. An mBANDing paint is composed of multiple overlapping subchromosomal probes

  2. Physiological and Pathological Transcriptional Activation of Endogenous Retroelements Assessed by RNA-Sequencing of B Lymphocytes

    Directory of Open Access Journals (Sweden)

    Jan Attig

    2017-12-01

    Full Text Available In addition to evolutionarily-accrued sequence mutation or deletion, endogenous retroelements (EREs in eukaryotic genomes are subject to epigenetic silencing, preventing or reducing their transcription, particularly in the germplasm. Nevertheless, transcriptional activation of EREs, including endogenous retroviruses (ERVs and long interspersed nuclear elements (LINEs, is observed in somatic cells, variably upon cellular differentiation and frequently upon cellular transformation. ERE transcription is modulated during physiological and pathological immune cell activation, as well as in immune cell cancers. However, our understanding of the potential consequences of such modulation remains incomplete, partly due to the relative scarcity of information regarding genome-wide ERE transcriptional patterns in immune cells. Here, we describe a methodology that allows probing RNA-sequencing (RNA-seq data for genome-wide expression of EREs in murine and human cells. Our analysis of B cells reveals that their transcriptional response during immune activation is dominated by induction of gene transcription, and that EREs respond to a much lesser extent. The transcriptional activity of the majority of EREs is either unaffected or reduced by B cell activation both in mice and humans, albeit LINEs appear considerably more responsive in the latter host. Nevertheless, a small number of highly distinct ERVs are strongly and consistently induced during B cell activation. Importantly, this pattern contrasts starkly with B cell transformation, which exhibits widespread induction of EREs, including ERVs that minimally overlap with those responsive to immune stimulation. The distinctive patterns of ERE induction suggest different underlying mechanisms and will help separate physiological from pathological expression.

  3. The histone methyltransferase SETDB1 represses endogenous and exogenous retroviruses in B lymphocytes.

    Science.gov (United States)

    Collins, Patrick L; Kyle, Katherine E; Egawa, Takeshi; Shinkai, Yoichi; Oltz, Eugene M

    2015-07-07

    Genome stability relies on epigenetic mechanisms that enforce repression of endogenous retroviruses (ERVs). Current evidence suggests that distinct chromatin-based mechanisms repress ERVs in cells of embryonic origin (histone methylation dominant) vs. more differentiated cells (DNA methylation dominant). However, the latter aspect of this model has not been tested. Remarkably, and in contrast to the prevailing model, we find that repressive histone methylation catalyzed by the enzyme SETDB1 is critical for suppression of specific ERV families and exogenous retroviruses in committed B-lineage cells from adult mice. The profile of ERV activation in SETDB1-deficient B cells is distinct from that observed in corresponding embryonic tissues, despite the loss of repressive chromatin modifications at all ERVs. We provide evidence that, on loss of SETDB1, ERVs are activated in a lineage-specific manner depending on the set of transcription factors available to target proviral regulatory elements. These findings have important implications for genome stability in somatic cells, as well as the interface between epigenetic repression and viral latency.

  4. B lymphocytes confer immune tolerance via cell surface GARP-TGF-β complex.

    Science.gov (United States)

    Wallace, Caroline H; Wu, Bill X; Salem, Mohammad; Ansa-Addo, Ephraim A; Metelli, Alessandra; Sun, Shaoli; Gilkeson, Gary; Shlomchik, Mark J; Liu, Bei; Li, Zihai

    2018-04-05

    GARP, a cell surface docking receptor for binding and activating latent TGF-β, is highly expressed by platelets and activated Tregs. While GARP is implicated in immune invasion in cancer, the roles of the GARP-TGF-β axis in systemic autoimmune diseases are unknown. Although B cells do not express GARP at baseline, we found that the GARP-TGF-β complex is induced on activated human and mouse B cells by ligands for multiple TLRs, including TLR4, TLR7, and TLR9. GARP overexpression on B cells inhibited their proliferation, induced IgA class-switching, and dampened T cell-independent antibody production. In contrast, B cell-specific deletion of GARP-encoding gene Lrrc32 in mice led to development of systemic autoimmune diseases spontaneously as well as worsening of pristane-induced lupus-like disease. Canonical TGF-β signaling more readily upregulates GARP in Peyer patch B cells than in splenic B cells. Furthermore, we demonstrated that B cells are required for the induction of oral tolerance of T cell-dependent antigens via GARP. Our studies reveal for the first time to our knowledge that cell surface GARP-TGF-β is an important checkpoint for regulating B cell peripheral tolerance, highlighting a mechanism of autoimmune disease pathogenesis.

  5. B-lymphocyte differentiation in lethally irradiated and reconstituted mice. II. Recovery of humoral immune responsiveness

    International Nuclear Information System (INIS)

    Rozing, J.; Brons, N.H.C.; Benner, R.

    1977-01-01

    The recovery of humoral immune responsiveness was studied in lethally irradiated, fetal liver-reconstituted mice. By means of both membrane fluorescence and antibody formation to sheep red blood cells (SRBC) as a functional assay, the rate of recovery of the compartments of B and T lymphocytes was determined in various lymphoid organs. The recovery of the immunoglobulin-positive (B) cell compartment after irradiation and reconstitution started in the spleen. This organ was also found to be the first in which the recovery of the B-cell population was completed. The interval between the recovery of the B-cell population in the spleen and that in the other organs tested was found to increase when the irradiated mice were reconstituted with spleen colony cells instead of fetal liver cells. This proved to be caused by the number and nature of the reconstituting hemopoietic stem cells. The immunoglobulin-positive (B) cells were found to appear before SRBC-reactive B cells could be demonstrated in spleen, lymph nodes, and Peyer's patches. The appearance of T lymphocytes in the various lymphoid organs required even more time. By means of cell transfer experiments, a sequential appearance of the precursors of anti-SRBC IgM-, IgG-, and IgA-plaque-forming cells could be demonstrated in spleen, bone marrow, lymph nodes, and Peyer's patches

  6. DC-SIGN on B lymphocytes is required for transmission of HIV-1 to T lymphocytes.

    Directory of Open Access Journals (Sweden)

    Giovanna Rappocciolo

    2006-07-01

    Full Text Available Infection of T cells by HIV-1 can occur through binding of virus to dendritic cell (DC-specific ICAM-3 grabbing nonintegrin (DC-SIGN on dendritic cells and transfer of virus to CD4+ T cells. Here we show that a subset of B cells in the blood and tonsils of normal donors expressed DC-SIGN, and that this increased after stimulation in vitro with interleukin 4 and CD40 ligand, with enhanced expression of activation and co-stimulatory molecules CD23, CD58, CD80, and CD86, and CD22. The activated B cells captured and internalized X4 and R5 tropic strains of HIV-1, and mediated trans infection of T cells. Pretreatment of the B cells with anti-DC-SIGN monoclonal antibody blocked trans infection of T cells by both strains of HIV-1. These results indicate that DC-SIGN serves as a portal on B cells for HIV-1 infection of T cells in trans. Transmission of HIV-1 from B cells to T cells through this DC-SIGN pathway could be important in the pathogenesis of HIV-1 infection.

  7. The immunoreceptor adapter protein DAP12 suppresses B lymphocyte?driven adaptive immune responses

    OpenAIRE

    Nakano-Yokomizo, Takako; Tahara-Hanaoka, Satoko; Nakahashi-Oda, Chigusa; Nabekura, Tsukasa; Tchao, Nadia K.; Kadosaki, Momoko; Totsuka, Naoya; Kurita, Naoki; Nakamagoe, Kiyotaka; Tamaoka, Akira; Takai, Toshiyuki; Yasui, Teruhito; Kikutani, Hitoshi; Honda, Shin-ichiro; Shibuya, Kazuko

    2011-01-01

    DAP12, an immunoreceptor tyrosine-based activation motif?bearing adapter protein, is involved in innate immunity mediated by natural killer cells and myeloid cells. We show that DAP12-deficient mouse B cells and B cells from a patient with Nasu-Hakola disease, a recessive genetic disorder resulting from loss of DAP12, showed enhanced proliferation after stimulation with anti-IgM or CpG. Myeloid-associated immunoglobulin-like receptor (MAIR) II (Cd300d) is a DAP12-associated immune receptor. L...

  8. The Role of mTOR Signaling in the Regulation of RAG Expression and Genomic Stability During B Lymphocyte Development

    Science.gov (United States)

    2014-07-01

    antibiotics (without IL-7) at 37°C in a 5% CO2 incubator. Cell lines and culture Jurkat cells, Abelson murine leukemia virus (Ab-MuLV) cells, or p210 BCR-Abl...effect of mTOR inhibi- tors on leukemia-cell proliferation and survival, in the present study, we treated human Jurkat T-ALL cells with rapamycin or the...dual PI3K/mTOR kinase inhibitor LY294002. We observed that rapamycin only slightly reduced Jurkat cell growth and had no effect on cell viability

  9. Effects of Bacillus Calmette-Guérin (BCG) vaccination at birth on T and B lymphocyte subsets

    DEFF Research Database (Denmark)

    Birk, Nina Marie; Nissen, Thomas Nørrelykke; Kjærgaard, Jesper

    2017-01-01

    , determined by flow cytometry. In 118 infants blood samples were obtained 4 (±2) days post randomization to BCG vaccination or no intervention, and at 3 and 13 months of age. No effects of BCG were found at 4 days. However, BCG increased proportions of effector memory cells at 3 months (Geometric mean ratio......The Bacillus Calmette-Guérin vaccine (BCG) has been associated with beneficial non-specific effects (NSEs) on infant health. Within a randomized trial on the effect of neonatal BCG on overall health, we investigated the possible immunological impact of neonatal BCG vaccination on lymphocyte subsets...... (GMR) 1.62, 95% confidence interval (CI) (1.20-2.21), p = 0.002 for CD4(+) T cells and GMR 1.69, 95% CI (1.06-2.70), p = 0.03 for CD8(+) T cells), and reduced proportions of late differentiated CD4(+) T cells (GMR = 0.62, 95% CI (0.38-1.00), p = 0.05) and apoptotic CD4(+) T cells at 13 months (GMR = 0...

  10. Enteroantigen (eAg)-binding B lymphocytes in the mouse - phenotype, distribution, function and eAg-specific antibody secretion

    DEFF Research Database (Denmark)

    Venning, Freja Albjerg; Trempenau, Mette Louise; Schmidt, Esben

    2013-01-01

    cells in causing proliferation of eAg-specific T cells. In comparison with eAg- B cells, eAg+ B cells secrete a significant amount of IL-10 in vitro, suggesting an anti-inflammatory potential. Compared with wild-type B cells, B cell receptor (BCR) transgenic, hen egg lysozyme-specific B cells show...... inferior eAg binding and T cell stimulatory activity suggesting involvement of the BCR in eAg binding and processing. After activation of CD19(+) B cells by eAg and hybridization with hypoxanthine-aminopterin-thymidine (HAT) sensitive ×63 lymphoma cells followed by cloning at limiting dilution conditions...

  11. Effect of gamma radiation on resting B lymphocytes. II. Functional characterization of the antigen-presentation defect

    International Nuclear Information System (INIS)

    Ashwell, J.D.; Jenkins, M.K.; Schwartz, R.H.

    1988-01-01

    The effect of radiation on three discrete Ag-presentation functions in resting B cells was examined: 1) Ag uptake and processing, 2) expression of processed Ag in the context of functional class II molecules, and 3) provision of necessary co-stimulatory, or second, signals. Analysis of radiation's effect on B cell presentation of intact vs fragmented Ag or its effect on presentation by Ag-pulsed B cells indicated that damage to Ag uptake and processing could not account for the bulk of the radiation-induced Ag-presentation defect. Experiments with phosphatidylinositol hydrolysis as an indirect measure of TCR occupancy suggested that irradiation caused a fairly rapid (within 1 to 2 h) decrease in the ability of the B cell APC to display a stimulatory combination of Ag and class II molecule. Ag dose-response analyses demonstrated that when presenting a fragment of the Ag pigeon cytochrome c to a T cell clone, 3000 rad-treated B cell APC were able to stimulate approximately 50% as much phosphatidylinositol turnover as unirradiated B cells. It was also found that, in contrast to their inability to initiate T cell proliferation, and similarly to chemically cross-linked splenocytes, heavily irradiated resting B cells plus Ag induced a state of Ag hyporesponsiveness in T cell clones. This effect on T cells had the same Ag- and MHC-specificity as did receptor occupancy required for proliferation, indicating that heavily irradiated resting B cells bear functional class II molecules. Co-culture of T cells with allogeneic B cells and syngeneic heavily irradiated B cells or chemically cross-linked splenic APC plus Ag resulted in T cell proliferation and interfered with the induction of the hyporesponsive state. This co-stimulatory function was radiosensitive in resting allogeneic B cells

  12. Transition pattern and mechanism of B-lymphocyte precursors in regenerated mouse bone marrow after subtotal body irradiation.

    Directory of Open Access Journals (Sweden)

    Deping Han

    Full Text Available Little is known about the effects of ionizing radiation on the transition and the related signal transduction of progenitor B cells in the bone marrow. Thus, using an NIH Swiss mouse model, we explored the impact of ionizing radiation on the early stage of B-cell development via an examination of the transition of CLP to pro-B to pre-B cells within bone marrow as a function of radiation doses and times. Our results showed that while the total number of bone marrow lymphoid cells at different stages were greatly reduced by subtotal body irradiation (sub-TBI, the surviving cells continued to transition from common lymphoid progenitors to pro-B and then to pre-B in a reproducible temporal pattern. The rearrangement of the immunoglobulin heavy chain increased significantly 1-2 weeks after irradiation, but no change occurred after 3-4 weeks. The rearrangement of the immunoglobulin light chain decreased significantly 1-2 weeks after sub-TBI but increased dramatically after 3-4 weeks. In addition, several key transcription factors and signaling pathways were involved in B-precursor transitions after sub-TBI. The data indicate that week 2 after irradiation is a critical time for the transition from pro-B cells to pre-B cells, reflecting that the functional processes for different B-cell stages are well preserved even after high-dose irradiation.

  13. POLYCHLORINATED BIPHENYL MIXTURES (AROCLORS) INHIBIT LPS-INDUCED MURINE B-LYMPHOCYTE PROLIFERATION IN VITRO. (R826687)

    Science.gov (United States)

    The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

  14. Protein sorting by lipid phase-like domains supports emergent signaling function in B lymphocyte plasma membranes.

    Science.gov (United States)

    Stone, Matthew B; Shelby, Sarah A; Núñez, Marcos F; Wisser, Kathleen; Veatch, Sarah L

    2017-02-01

    Diverse cellular signaling events, including B cell receptor (BCR) activation, are hypothesized to be facilitated by domains enriched in specific plasma membrane lipids and proteins that resemble liquid-ordered phase-separated domains in model membranes. This concept remains controversial and lacks direct experimental support in intact cells. Here, we visualize ordered and disordered domains in mouse B lymphoma cell membranes using super-resolution fluorescence localization microscopy, demonstrate that clustered BCR resides within ordered phase-like domains capable of sorting key regulators of BCR activation, and present a minimal, predictive model where clustering receptors leads to their collective activation by stabilizing an extended ordered domain. These results provide evidence for the role of membrane domains in BCR signaling and a plausible mechanism of BCR activation via receptor clustering that could be generalized to other signaling pathways. Overall, these studies demonstrate that lipid mediated forces can bias biochemical networks in ways that broadly impact signal transduction.

  15. Targeted deletion of the tachykinin 4 gene (TAC4-/-) influences the early stages of B lymphocyte development.

    Science.gov (United States)

    Berger, Alexandra; Benveniste, Patricia; Corfe, Steven A; Tran, Anne H; Barbara, Mary; Wakeham, Andrew; Mak, Tak W; Iscove, Norman N; Paige, Christopher J

    2010-11-11

    Hemokinin-1 (HK-1), encoded by the TAC4 gene, is a tachykinin peptide that is predominantly expressed in non-neuronal cells, such as immune cells. We have disrupted the mouse TAC4 gene to obtain a better understanding of the actions of HK-1 during hematopoiesis. We demonstrate here that TAC4(-/-) mice exhibit an increase of CD19(+)CD117(+)HSA(+)BP.1(-) "fraction B" pro-B cells in the bone marrow, whereas pre-B, immature, and mature B cells are within the normal range. We show that in vitro cultures derived from TAC4(-/-) bone marrow, sorted "fraction B" pro-B cells or purified long-term reconstituting stem cells, contain significantly higher numbers of pro-B cells compared with controls, suggesting an inhibitory role for HK-1 on developing B cells. Supporting this idea, we show that addition of HK-1 to cultures established from long-term reconstituting stem cells and the newly described intermediate-term reconstituting stem cells leads to a significant decrease of de novo generated pro-B cells. Based on our studies, we postulate that HK-1 plays an inhibitory role in hematopoiesis, and we hypothesize that it may be part of the bone marrow microenvironment that supports and regulates the proliferation and differentiation of hematopoietic cells.

  16. Presence of Recently Activated B Lymphocytes in Chicken Gut Associated Lymphoid Tissue after an Ascaridia galli Infection

    DEFF Research Database (Denmark)

    Norup, L. R.; Dalgaard, T. S.; Pleidrup, J.

    2013-01-01

    The causative agent of tuberculosis, Mycobacterium tuberculosis, has infected over a third of the world's population and poses a massive burden to health care systems and human well-being. Most M. tuberculosis infections are latent and are not cleared fully by the host immune system due to the hi...

  17. The Planar Cell Polarity Pathway Drives Pathogenesis of Chronic Lymphocytic Leukemia by the Regulation of B-Lymphocyte Migration

    Czech Academy of Sciences Publication Activity Database

    Kaucká, M.; Plevová, K.; Pavlová, Š.; Janovská, P.; Mishra, A.; Verner, J.; Procházková, J.; Krejčí, Pavel; Kotásková, J.; Ovesná, P.; Tichý, B.; Brychtová, Y.; Doubek, M.; Kozubík, Alois; Mayer, J.; Pospíšilová, Š.; Bryja, Vítězslav

    2013-01-01

    Roč. 73, č. 5 (2013), s. 1491-1501 ISSN 0008-5472 R&D Projects: GA ČR(CZ) GD204/09/H058 Grant - others:GA ČR(CZ) GAP301/11/0747; GA ČR(CZ) GAP305/11/0752; GA MŠk(CZ) LH12004; GA MŠk(CZ) ED1.1.00/02.0068 Program:GA; ED Institutional support: RVO:68081707 Keywords : KINASE-I-EPSILON * SURVIVAL SIGNALS * INHIBITOR Subject RIV: BO - Biophysics Impact factor: 9.284, year: 2013

  18. Complement receptor expression and activation of the complement cascade on B lymphocytes from patients with systemic lupus erythematosus (SLE)

    DEFF Research Database (Denmark)

    Marquart, H V; Svendsen, A; Rasmussen, J M

    1995-01-01

    receptors and regulatory proteins on B cells from SLE patients, as well as the deposition of C3 fragments occurring in vivo or after in vitro AP activation. We have confirmed, for a proportion of the patients studied, reduced expression of CR1 and CR2 on B cells, and shown a consistency between low CR2...... activation by B cells in homologous serum. Finally, we demonstrated an inverse relationship between SLE disease activity index (SLEDAI) and the expression of complement receptor 2 (CR2) on SLE B cells. Thus, determination of CR2 on B cells may emerge as an additional laboratory tool in the assessment of SLE...

  19. Detection of newly produced T and B lymphocytes by digital PCR in blood stored dry on nylon flocked swabs.

    Science.gov (United States)

    Tessitore, Marion Vaglio; Sottini, Alessandra; Roccaro, Aldo M; Ghidini, Claudia; Bernardi, Simona; Martellosio, Giovanni; Serana, Federico; Imberti, Luisa

    2017-04-05

    A normal number of T-cell receptor excision circles (TRECs) and K-deleting recombination excision circles (KRECs) is considered a biomarker for adequate new T- and B-cell production. In newborns, detection of TRECs and KRECs by real time PCR from dried blood spotted on filter paper is used for the screening of severe immunodeficiency. In adults, elderly and during diseases, where the number of TRECs is lower than in newborns and children, a large amount of DNA and a sensitive method of amplification are necessary to identify newly produced lymphocytes. DNA was prepared from blood of 203 healthy adults (range: 18-91 years old) absorbed for 10 s on flocked swabs and let to dry, or from peripheral blood mononuclear cells. DNA was subjected to digital PCR and to well established conventional real time PCR-based method using TREC- and KREC-specific primers and probes. The number of TRECs and KRECs was expressed per mL of blood. Statistical analysis was performed by nested ANOVA, Pearson coefficient of determination, and by linear regression tests. The novel method for the storage of dried blood on nylon flocked swabs and the use of digital PCR allow quantification of TRECs and KRECs with high degree of sensitivity, specificity, accuracy, and precision. TRECs and KRECs were amplified by digital PCR in all tested blood samples, including those obtained from elderly individuals (>70 years old) and that were negative by real time PCR. Furthermore, values of TRECs and KRECs obtained by digital PCR were in the range of those acquired by real time PCR. Our findings demonstrate that DNA isolation from dried blood on flocked swabs followed by digital PCR-based analysis represents a useful tool for studying new lymphocyte production in adults and elderly individuals. This suggests the potential use of the methodology when monitoring of clinical variables is limited by the number of molecules that can be amplified and detected, such as in patients with immunodeficiency or under immunosuppressive therapies.

  20. Molecular characterization of CD9 and CD63, two tetraspanin family members expressed in trout B lymphocytes.

    Science.gov (United States)

    Castro, Rosario; Abós, Beatriz; González, Lucia; Aquilino, Carolina; Pignatelli, Jaime; Tafalla, Carolina

    2015-07-01

    Tetraspanins are a family of membrane-organizing proteins, characterized by the presence of four highly conserved transmembrane regions that mediate diverse physiological functions. In the current study, we have identified two novel tetraspanin members in rainbow trout (Oncorhynchus mykiss), homologs to mammalian CD9 and CD63. Both genes were expressed in muscle, skin, gills, hindgut, gonad, liver, spleen, head kidney, thymus and peripheral blood leukocytes. Throughout the early life cycle stages, CD9 mRNA levels significantly increased after first feeding, whereas CD63 transcription remained constant during all the developmental stages analyzed. In response to an experimental bath infection with viral hemorrhagic septicemia virus (VHSV), CD9 transcription was down-regulated in the gills, while CD63 mRNA levels were down-regulated in the head kidney. Instead, when the virus was intraperitoneally injected, the transcription of both genes was significantly up-regulated in peritoneal cells at several days post-infection. Additionally, both genes were transcriptionally up-regulated in the muscle of trout injected with a VHSV DNA vaccine. To gain insight on the relation of these tetraspanins with B cell activity we determined their constitutive expression in naive IgM(+) populations from different sources and observed that both molecules were being transcribed by IgM(+) cells in different tissues. Furthermore, CD9 transcription was significantly down-regulated in splenic IgM(+) cells in response to in vitro VHSV exposure. Our results provide insights on the potential role of these tetraspanins on teleost B cell and antiviral immunity. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. Brief communication: evidence that B lymphocytes carry the nuclear pocket abnormality associated with bovine leukemia virus infection

    Energy Technology Data Exchange (ETDEWEB)

    Pomeroy, K.A.; Paul, P.S.; Weber, A.F.; Sorensen, D.K.; Johnson, D.W.

    1976-01-01

    Peripheral blood lymphocytes from three cows with persistent lymphocytosis were separated on nylon wool columns into nylon wool adherent and nonadherent populations. The percentage of cells coated with surface immunoglobulin and the frequency of lymphocytic nuclear pockets in each subpopulation were then determined. In each case the adherent population consisted predominantly of B cells with an increased nuclear pocket frequency while the non-adherent cells were 98 to 99 percent surface immunoglobulin negative and contained essentially no nuclear pockets. These findings provide additional evidence that the B subpopulation of cells is highly involved in bovine leukemia oncogenesis.

  2. Complement receptor expression and activation of the complement cascade on B lymphocytes from patients with systemic lupus erythematosus (SLE)

    DEFF Research Database (Denmark)

    Marquart, H V; Svendsen, A; Rasmussen, J M

    1995-01-01

    It has previously been reported that the expression of the complement receptors, CR1 on erythrocytes and blood leucocytes and CR2 on B cells, is reduced in patients with SLE, and that the reduced expression of CR1 on erythrocytes is related to disease activity. We have earlier demonstrated...... that normal B cells are capable of activating the alternative pathway (AP) of complement in a CR2-dependent fashion. In this study we have investigated whether disturbances in this activity may be related to the altered phenotype of SLE B cells. Flow cytometry was used to measure expression of complement...... activation by B cells in homologous serum. Finally, we demonstrated an inverse relationship between SLE disease activity index (SLEDAI) and the expression of complement receptor 2 (CR2) on SLE B cells. Thus, determination of CR2 on B cells may emerge as an additional laboratory tool in the assessment of SLE...

  3. Plasmodium chabaudi in mice. Adoptive transfer of immunity with enriched populations of spleen T and B lymphocytes

    International Nuclear Information System (INIS)

    McDonald, V.; Phillips, R.S.

    1978-01-01

    Thymectomized NIH and C57BL mice were more susceptible to Plasmodium chabaudi than controls, indicating a role for T cells in acquired immunity to the parasite. Enriched populations of T and B cells were prepared from the spleens of immune mice using nylon-wool columns, and were adoptively transferred to syngeneic non-irradiated mice or mice irradiated with 600 or 800 rad. Some immunity could usually be transferred with immune T, B and glass-wool (g.w.) filtered spleen cell populations. In the heavily irradiated mice g.w. filtered immune spleen cells gave the best protection and the immune T cells the least. Preliminary attempts to show synergistic activity between immune T and B cells in irradiated mice were not successful. (author)

  4. A systems toxicology approach identifies Lyn as a key signaling phosphoprotein modulated by mercury in a B lymphocyte cell model

    Energy Technology Data Exchange (ETDEWEB)

    Caruso, Joseph A.; Stemmer, Paul M. [Institute of Environmental Health Sciences, Wayne State University, Detroit, MI (United States); Dombkowski, Alan [Department of Pediatrics, Wayne State University, Detroit, MI (United States); Caruthers, Nicholas J. [Institute of Environmental Health Sciences, Wayne State University, Detroit, MI (United States); Gill, Randall [Department of Immunology and Microbiology, Wayne State University, Detroit, MI (United States); Rosenspire, Allen J., E-mail: arosenspire@wayne.edu [Department of Immunology and Microbiology, Wayne State University, Detroit, MI (United States)

    2014-04-01

    Network and protein–protein interaction analyses of proteins undergoing Hg{sup 2+}-induced phosphorylation and dephosphorylation in Hg{sup 2+}-intoxicated mouse WEHI-231 B cells identified Lyn as the most interconnected node. Lyn is a Src family protein tyrosine kinase known to be intimately involved in the B cell receptor (BCR) signaling pathway. Under normal signaling conditions the tyrosine kinase activity of Lyn is controlled by phosphorylation, primarily of two well known canonical regulatory tyrosine sites, Y-397 and Y-508. However, Lyn has several tyrosine residues that have not yet been determined to play a major role under normal signaling conditions, but are potentially important sites for phosphorylation following mercury exposure. In order to determine how Hg{sup 2+} exposure modulates the phosphorylation of additional residues in Lyn, a targeted MS assay was developed. Initial mass spectrometric surveys of purified Lyn identified 7 phosphorylated tyrosine residues. A quantitative assay was developed from these results using the multiple reaction monitoring (MRM) strategy. WEHI-231 cells were treated with Hg{sup 2+}, pervanadate (a phosphatase inhibitor), or anti-Ig antibody (to stimulate the BCR). Results from these studies showed that the phosphoproteomic profile of Lyn after exposure of the WEHI-231 cells to a low concentration of Hg{sup 2+} closely resembled that of anti-Ig antibody stimulation, whereas exposure to higher concentrations of Hg{sup 2+} led to increases in the phosphorylation of Y-193/Y-194, Y-501 and Y-508 residues. These data indicate that mercury can disrupt a key regulatory signal transduction pathway in B cells and point to phospho-Lyn as a potential biomarker for mercury exposure. - Highlights: • Inorganic mercury (Hg{sup 2+}) induces changes in the WEHI-231 B cell phosphoproteome. • The B cell receptor (BCR) signaling pathway was the pathway most affected by Hg{sup 2+}. • The Src family phosphoprotein kinase Lyn was the most interconnected node. • Lyn is likely central to the immunotoxic potential of Hg{sup 2+}. • Lyn phosphorylation profiles may be biomarkers for Hg{sup 2+} intoxication of B cells.

  5. Grb2 and the non-T cell activation linker NTAL constitute a Ca(2+)-regulating signal circuit in B lymphocytes

    Czech Academy of Sciences Publication Activity Database

    Stork, B.; Engelke, M.; Frey, J.; Hořejší, Václav; Hamm-Baarke, A.; Schraven, B.; Kurosaki, T.; Wienands, J.

    2004-01-01

    Roč. 21, č. 5 (2004), s. 681-691 ISSN 1074-7613 R&D Projects: GA MŠk LN00A026 Institutional research plan: CEZ:AV0Z5052915 Keywords : NTAL * Grb2 * lymphocyte Subject RIV: EC - Immunology Impact factor: 15.448, year: 2004

  6. Is there a role for B lymphocyte chimerism in the monitoring of B-acute lymphoblastic leukemia patients receiving allogeneic stem cell transplantation?

    Directory of Open Access Journals (Sweden)

    Yi-Ning Yang

    2015-03-01

    Full Text Available Objective: To determine the sensitivity and significance of B-cell chimerism for the detection of early engraftment, transplant rejection, and disease relapse. Methods: The dynamic monitoring of lineage-specific cell subtypes (B, T, and NK cells was made in 20 B-cell acute lymphoblastic leukemia (B-ALL patients following allogeneic hematopoietic stem cell transplantation (allo-HSCT. In the early period after allo-HSCT, the latest establishment of B-cell complete chimerism (CC was observed in a majority of patients. Results: The percentage of donor cells of B-cell lineage was lower than the percent of T-cell lineage in most of the mixed chimerism (MC patients. During graft rejection, the frequency of patients with decreasing MC of B-, T- and NK-cell lineage were 5/5, 2/5, and 2/5. When disease relapsed, five patients showed a faster decrease of the donor percent of B-cells than of T- or NK-cells. Only one patient displayed a more rapid decrease in NK-cells than in T- or B-cells. Conclusion: Monitoring of B-cell chimerism after HSCT seems to be valuable for insuring complete engraftment, anticipating graft rejection, and relapse in B-ALL patients. Keywords: B cell acute lymphoblastic leukemia (B-ALL, B-cell, T-cell, Chimerism, Allogeneic hematopoietic stem cell transplantation (allo-HSCT

  7. Antibody responses to allergen Lol pIV are suppressed following adoptive transfer of B lymphocytes from the internal image anti-idiotypic antibody-treated mice.

    Science.gov (United States)

    Zhou, E M; Kisil, F T

    1995-10-01

    An internal image anti-idiotypic antibody, designated B1/1, was generated against an idiotope (Id91) of the monoclonal antibody (mAb91) specific for Lol pIV. The administration of B1/1 in PBS, at doses ranging from 100 ng to 100 micrograms/mouse, to syngeneic Balb/c mice resulted in the suppression of the formation of anti-Lol pIV antibodies that possessed the Id91. Spleen cells obtained from the mice 2 weeks after the treatment with B1/1 (25 micrograms/mouse) were adoptively transferred intravenously into the syngeneic recipients which were challenged intraperitoneally with Lol pIV in alum 2 hr after the transfer. The recipients were boosted with Lol pIV 14 days later. It was demonstrated that the transfer of splenic B cells (but not of T cells) from B1/1-treated donors induced a significant suppression of not only the level of IgE and IgG antibodies to Lol pIV, but also the level of antibodies possessing the Id91. Treatment of the B cells with mAb91 plus complement abrogated their ability to transfer the suppression. This study indicates that the treatment with the anti-Id B1/1 generated B cells that were characterized, serologically, as possessing the anti-Id-like antibodies on their surface and were responsible for transferring the suppression of the formation of antibodies to allergen Lol pIV and the expression of Id91.

  8. CD40 Ligand (CD154) Incorporated into HIV Virions Induces Activation-Induced Cytidine Deaminase (AID) Expression in Human B Lymphocytes

    Science.gov (United States)

    Epeldegui, Marta; Thapa, Dharma R.; De La Cruz, Justin; Kitchen, Scott; Zack, Jerome A.; Martínez-Maza, Otoniel

    2010-01-01

    Most AIDS-associated non-Hodgkin's lymphoma (AIDS-NHL) arises from errors in immunoglobulin heavy-chain gene (IgH) class switch recombination (CSR) or somatic hypermutation (SHM), events that occur in germinal center (GC) B cells and require the activity of activation induced cytidine deaminase (AID). Several oncogenic viruses (EBV, HCV, HPV) can induce AID gene (AID) expression, and elevated AID expression is seen in circulating lymphocytes prior to AIDS-NHL diagnosis. Here, we report that HIV produced in peripheral blood mononuclear cells (PBMC) induced AID expression in normal human B cells. Since HIV produced in PBMC contains host cell CD40 ligand (CD40L) incorporated into the viral membrane, and CD40L is known to induce AID expression in human B cells, the role of virion-associated CD40L in HIV-induced AID expression was examined. Only viruses expressing functional CD40L were seen to induce AID expression; CD40L-negative HIV did not induce AID expression. The induction of AID expression by CD40L+ HIV was abrogated by addition of blocking anti-CD40L antibody. AID protein was detected in B cells exposed to CD40L+ HIV using intracellular multicolor flow cytometry, with most AID producing B cells expressing the CD71 activation marker on their surface. Therefore, HIV virions that express CD40L induce AID expression in B cells, and this induction appears to be due to a direct interaction between CD40L on these viruses and CD40 on B cells. These findings are consistent with a role for HIV in the direct stimulation of B cells, potentially leading to the accumulation of molecular lesions that have the potential to contribute to the development of NHL. PMID:20625427

  9. CD40 ligand (CD154 incorporated into HIV virions induces activation-induced cytidine deaminase (AID expression in human B lymphocytes.

    Directory of Open Access Journals (Sweden)

    Marta Epeldegui

    2010-07-01

    Full Text Available Most AIDS-associated non-Hodgkin's lymphoma (AIDS-NHL arises from errors in immunoglobulin heavy-chain gene (IgH class switch recombination (CSR or somatic hypermutation (SHM, events that occur in germinal center (GC B cells and require the activity of activation induced cytidine deaminase (AID. Several oncogenic viruses (EBV, HCV, HPV can induce AID gene (AID expression, and elevated AID expression is seen in circulating lymphocytes prior to AIDS-NHL diagnosis. Here, we report that HIV produced in peripheral blood mononuclear cells (PBMC induced AID expression in normal human B cells. Since HIV produced in PBMC contains host cell CD40 ligand (CD40L incorporated into the viral membrane, and CD40L is known to induce AID expression in human B cells, the role of virion-associated CD40L in HIV-induced AID expression was examined. Only viruses expressing functional CD40L were seen to induce AID expression; CD40L-negative HIV did not induce AID expression. The induction of AID expression by CD40L+ HIV was abrogated by addition of blocking anti-CD40L antibody. AID protein was detected in B cells exposed to CD40L+ HIV using intracellular multicolor flow cytometry, with most AID producing B cells expressing the CD71 activation marker on their surface. Therefore, HIV virions that express CD40L induce AID expression in B cells, and this induction appears to be due to a direct interaction between CD40L on these viruses and CD40 on B cells. These findings are consistent with a role for HIV in the direct stimulation of B cells, potentially leading to the accumulation of molecular lesions that have the potential to contribute to the development of NHL.

  10. Dichotomy between factors inducing the immunosuppressive enzyme IL-4-induced gene 1 (IL4I1) in B lymphocytes and mononuclear phagocytes.

    Science.gov (United States)

    Marquet, Jeanine; Lasoudris, Fanette; Cousin, Céline; Puiffe, Marie-Line; Martin-Garcia, Nadine; Baud, Véronique; Chereau, Fanny; Farcet, Jean-Pierre; Molinier-Frenkel, Valérie; Castellano, Flavia

    2010-09-01

    MPhi and DC are key elements in the control of tissue homeostasis and response to insult. In this work, we demonstrate that MPhi and DC are the major producers of the phenylalanine catabolizing enzyme IL-4-induced gene 1 (IL4I1) under inflammatory conditions. IL4I1 was first described in B cells, which indeed can produce IL4I1 in vitro, although at much lower levels. In vivo, IL4I1 is highly expressed by MPhi and DC of Th1 granulomas (sarcoidosis, tuberculosis) but poorly detected in Th2 granulomas (schistosomiasis). In vitro, expression of the enzyme is induced in mononuclear phagocytes by various pro-inflammatory stimuli through the activation of the transcription factors NF-kappaB and/or STAT1. B cells also express IL4I1 in response to NF-kappaB-activating stimuli such as CD40L; however, in contrast to myeloid cells, B cells are insensitive to IFN-gamma but respond to stimulation of the IL-4/STAT6 axis. As we show that the expression of IL4I1 by a monocytic cell line inhibits T-cell proliferation and production of IFN-gamma and inflammatory cytokines, we propose that IL4I1 participates in the downregulation of Th1 inflammation in vivo.

  11. Optimization of proximity ligation assay (PLA) for detection of protein interactions and fusion proteins in non-adherent cells: application to pre-B lymphocytes.

    Science.gov (United States)

    Debaize, Lydie; Jakobczyk, Hélène; Rio, Anne-Gaëlle; Gandemer, Virginie; Troadec, Marie-Bérengère

    2017-01-01

    Genetic abnormalities, including chromosomal translocations, are described for many hematological malignancies. From the clinical perspective, detection of chromosomal abnormalities is relevant not only for diagnostic and treatment purposes but also for prognostic risk assessment. From the translational research perspective, the identification of fusion proteins and protein interactions has allowed crucial breakthroughs in understanding the pathogenesis of malignancies and consequently major achievements in targeted therapy. We describe the optimization of the Proximity Ligation Assay (PLA) to ascertain the presence of fusion proteins, and protein interactions in non-adherent pre-B cells. PLA is an innovative method of protein-protein colocalization detection by molecular biology that combines the advantages of microscopy with the advantages of molecular biology precision, enabling detection of protein proximity theoretically ranging from 0 to 40 nm. We propose an optimized PLA procedure. We overcome the issue of maintaining non-adherent hematological cells by traditional cytocentrifugation and optimized buffers, by changing incubation times, and modifying washing steps. Further, we provide convincing negative and positive controls, and demonstrate that optimized PLA procedure is sensitive to total protein level. The optimized PLA procedure allows the detection of fusion proteins and protein interactions on non-adherent cells. The optimized PLA procedure described here can be readily applied to various non-adherent hematological cells, from cell lines to patients' cells. The optimized PLA protocol enables detection of fusion proteins and their subcellular expression, and protein interactions in non-adherent cells. Therefore, the optimized PLA protocol provides a new tool that can be adopted in a wide range of applications in the biological field.

  12. Effects of Bacillus Calmette-Guérin (BCG) vaccination at birth on T and B lymphocyte subsets: Results from a clinical randomized trial.

    Science.gov (United States)

    Birk, Nina Marie; Nissen, Thomas Nørrelykke; Kjærgaard, Jesper; Hartling, Hans Jacob; Thøstesen, Lisbeth Marianne; Kofoed, Poul-Erik; Stensballe, Lone Graff; Andersen, Andreas; Pryds, Ole; Netea, Mihai G; Benn, Christine Stabell; Nielsen, Susanne Dam; Jeppesen, Dorthe Lisbeth

    2017-09-29

    The Bacillus Calmette-Guérin vaccine (BCG) has been associated with beneficial non-specific effects (NSEs) on infant health. Within a randomized trial on the effect of neonatal BCG on overall health, we investigated the possible immunological impact of neonatal BCG vaccination on lymphocyte subsets, determined by flow cytometry. In 118 infants blood samples were obtained 4 (±2) days post randomization to BCG vaccination or no intervention, and at 3 and 13 months of age. No effects of BCG were found at 4 days. However, BCG increased proportions of effector memory cells at 3 months (Geometric mean ratio (GMR) 1.62, 95% confidence interval (CI) (1.20-2.21), p = 0.002 for CD4 + T cells and GMR 1.69, 95% CI (1.06-2.70), p = 0.03 for CD8 + T cells), and reduced proportions of late differentiated CD4 + T cells (GMR = 0.62, 95% CI (0.38-1.00), p = 0.05) and apoptotic CD4 + T cells at 13 months (GMR = 0.55, 95% CI (0.32-0.92), p = 0.03). In conclusion, limited overall impact of neonatal BCG vaccination on lymphocyte subsets was found in healthy Danish infants within the first 13 months of life. This is in line with the limited clinical effects of BCG observed in our setting.

  13. Effects of Bacillus Calmette-Guerin (BCG) vaccination at birth on T and B lymphocyte subsets: Results from a clinical randomized trial

    NARCIS (Netherlands)

    Birk, N.M.; Nissen, T.N.; Kjaergaard, J.; Hartling, H.J.; Thostesen, L.M.; Kofoed, P.E.; Stensballe, L.G.; Andersen, A.; Pryds, O.; Netea, M.G.; Benn, C.S.; Nielsen, S.D.; Jeppesen, D.L.

    2017-01-01

    The Bacillus Calmette-Guerin vaccine (BCG) has been associated with beneficial non-specific effects (NSEs) on infant health. Within a randomized trial on the effect of neonatal BCG on overall health, we investigated the possible immunological impact of neonatal BCG vaccination on lymphocyte subsets,

  14. Different anti-CD21 antibodies can be used to discriminate developmentally and functionally different subsets of B lymphocytes in circulation of pigs

    Czech Academy of Sciences Publication Activity Database

    Šinkora, Marek; Štěpánová, Kateřina; Šinkorová, Jana

    2013-01-01

    Roč. 39, č. 4 (2013), s. 409-418 ISSN 0145-305X R&D Projects: GA ČR GAP502/10/0038; GA MŠk ME09089 Institutional support: RVO:61388971 Keywords : Porcine immune system * Cell surface molecules * Lymphocyte subpopulations Subject RIV: EC - Immunology Impact factor: 3.705, year: 2013

  15. Developmental fate of hematopoietic stem cells: the study of individual hematopoietic clones at the level of antigen-responsive B lymphocytes.

    Science.gov (United States)

    Olovnikova, Natalia I; Drize, Nina J; Ershler, Maxim A; Nifontova, Irina N; Belkina, Elena V; Nikolaeva, Tatiana N; Proskurina, Natalia V; Chertkov, Joseph L

    2003-01-01

    We have shown previously that hematopoiesis in mice reconstituted with retrovirally marked hematopoietic stem cells (HSCs) is provided by multiple, mainly short-lived clones, as measured by retroviral insertion site analysis of individual spleen colony-forming unit (CFU-S)-derived colonies. However, the CFU-S is the relatively early progenitor and the contribution of each CFU-S in the steady-state hematopoiesis is uncertain. Here, we have studied the fate of individual mature B cells, as well as CFU-S, representing the progeny of retrovirally transduced marrow-repopulating cells (MRC). B-cells-generated hybridomas and CFU-S-derived colonies were used to determine the clonal composition of hematolymphopoiesis at the single-cell level. Bone marrow (BM) cells and splenocytes (approximately 1/3-1/2 of spleen at a time) from mice reconstituted with retrovirally marked syngeneic BM cells were repeatedly collected at 3, 10, and 16 months post-transplant. The percentage of retrovirally marked CFU-S and B-cell-produced hybridomas was about 50% at 3 months and decreased to 10-15% at 10 months after reconstitution in spite of stable degree of chimerism. The clonal origin of BM-derived CFU-S and spleen-derived B-cell hybridomas was detected by Southern blot analysis. Overall, DNA obtained from 159 retrovirally marked spleen colonies, 287 hybridomas and 43 BM samples were studied. Multiple simultaneously functioning clones of MRC-derived B cells were observed. The same individual clones among hybridomas and CFU-S were identified in three out of 11 mice. Thus, hematopoiesis is generated by multiple hematopoietic clones some of which can simultaneously contribute to both mature lymphoid cells and myeloid progenitors. These data establish that the stem cell compartment functions by continuously producing progeny, which fully but transiently repopulate all lineages.

  16. Radiosensitivity of T and B lymphocytes. IV. Effect of whole body irradiation upon various lymphoid tissues and numbers of recirculating lymphocytes

    International Nuclear Information System (INIS)

    Anderson, R.E.; Olson, G.B.; Autry, J.R.; Howarth, J.L.; Troup, G.M.; Bartels, P.H.

    1977-01-01

    Groups of 10-week-old-female CBA/J mice were exposed in whole body fashion to 0, 5, 50, and 500 rads and sacrificed in serial fashion 1, 3, 5, 7, 9, 15, and 30 days after irradiation for morphologic evaluation of thymus, spleen, lymph node, and Peyer's patch, and assessment of the relative numbers of thymus-derived (T) and bone marrow-derived (B) cells in these tissues. The absolute and relative numbers of recirculating T and B cells mobilizable by thoracic duct cannulation were also determined and compared with similar determinations with respect to peripheral blood lymphocytes. B cell depletion occurred more quickly and was more pronounced in spleen and lymph node than T cell depletion at all three exposure doses. Depletion of T and B cells was roughly equal in peripheral blood and thoracic duct lymph. When present, regeneration of the T cell component occurred more rapidly than did B cell restoration. The latter often was incomplete at the time of the final sacrifice (day 30). PHA-responsive and Con A-responsive cells also appeared to differ with respect to the kinetics of cell death after whole body irradiation

  17. IL-7 treatment augments and prolongs sepsis-induced expansion of IL-10-producing B lymphocytes and myeloid-derived suppressor cells.

    Science.gov (United States)

    Kulkarni, Upasana; Herrmenau, Christoph; Win, Stephanie J; Bauer, Michael; Kamradt, Thomas

    2018-01-01

    Immunological dysregulation in sepsis is associated with often lethal secondary infections. Loss of effector cells and an expansion of immunoregulatory cell populations both contribute to sepsis-induced immunosuppression. The extent and duration of this immunosuppression are unknown. Interleukin 7 (IL-7) is important for the maintenance of lymphocytes and can accelerate the reconstitution of effector lymphocytes in sepsis. How IL-7 influences immunosuppressive cell populations is unknown. We have used the mouse model of peritoneal contamination and infection (PCI) to investigate the expansion of immunoregulatory cells as long-term sequelae of sepsis with or without IL-7 treatment. We analysed the frequencies and numbers of regulatory T cells (Tregs), double negative T cells, IL-10 producing B cells and myeloid-derived suppressor cells (MDSCs) for 3.5 months after sepsis induction. Sepsis induced an increase in IL-10+ B cells, which was enhanced and prolonged by IL-7 treatment. An increased frequency of MDSCs in the spleen was still detectable 3.5 months after sepsis induction and this was more pronounced in IL-7-treated mice. MDSCs from septic mice were more potent at suppressing T cell proliferation than MDSCs from control mice. Our data reveal that sepsis induces a long lasting increase in IL-10+ B cells and MDSCs. Late-onset IL-7 treatment augments this increase, which should be relevant for clinical interventions.

  18. The improvement effects of edible bird’s nest on proliferation and activation of B lymphocyte and its antagonistic effects on immunosuppression induced by cyclophosphamide

    Directory of Open Access Journals (Sweden)

    Zhao R

    2016-01-01

    Full Text Available Ran Zhao,1,* Geng Li,1,* Xiu-juan Kong,1 Xiu-yan Huang,2 Wei Li,1 Yao-ying Zeng,2 Xiao-ping Lai31Traditional Chinese Medicinal College, Guangzhou University of Chinese Medicine, 2Life Science College, Jinan University, Guangzhou, 3Dongguan Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Dongguan, People’s Republic of China*These authors contributed equally to this workAbstract: Edible bird’s nest (EBN is regarded as an immune-enhancing food in the People’s Republic of China. The aim of this study is to demonstrate the efficiency of EBN in improving the immunity of mouse both in vivo and in vitro. We observed the effects of EBN on spleen lymphocytes proliferation and activation, as well as immunoglobulin isotypes as indicators. In addition, we evaluated the content of total sIgA in the intestinal juice to assess mucosal immunity. The results showed that EBN could promote the proliferation and activation of B-cells and increase IgE, IgA, IgM, and IgG3 levels. We also found that EBN extract can promote the secretion of sIgA in the small intestine. Using cyclophosphamide (CY, we established an immunosuppressed mouse model in which we identified a reversal influence on the ratio of CD3+/CD19+ cells, which indicates that EBN also protects B-cells from the damage induced by CY. We also applied polymyxin B to exclude the interference of lipopolysaccharide throughout the experiment. In conclusion, we found that EBN can reduce the intestinal immune injury induced by CY by accelerating the proliferation and activation of B-cells and enhancing antibody secretion of B-cells.Keywords: chemotherapy, immunological enhancement, intestinal mucosal immune, EBN

  19. Induction of DNA repair synthesis in human monocytes/B-lymphocytes compared with T-lymphocytes after exposure to N-acetoxy-N-acetylaminofluorene and dimethylsulfate in vitro

    DEFF Research Database (Denmark)

    Knudsen, Lisbeth E.; Ryder, L P; Wassermann, K

    1992-01-01

    We have explored the induction of DNA repair synthesis in monocyte/B- and T-lymphocyte enriched cell fractions from 12 different human mononuclear blood cell populations. Unscheduled DNA synthesis was measured in monocyte/B- and T-cells after exposure to the DNA-damaging agents dimethylsulfate (D...

  20. Impact of the B Cell Growth Factor APRIL on the Qualitative and Immunological Characteristics of Atherosclerotic Plaques

    NARCIS (Netherlands)

    Bernelot Moens, Sophie J.; van Leuven, Sander I.; Zheng, Kang H.; Havik, Stefan R.; Versloot, Miranda V.; van Duivenvoorde, Leonie M.; Hahne, Michael; Stroes, Erik S. G.; Baeten, Dominique L.; Hamers, Anouk A. J.

    2016-01-01

    Studies on the role of B lymphocytes in atherosclerosis development, have yielded contradictory results. Whereas B lymphocyte-deficiency aggravates atherosclerosis in mice; depletion of mature B lymphocytes reduces atherosclerosis. These observations led to the notion that distinct B lymphocyte

  1. Differential regulation of expression of the MHC class II molecules RT1.B and RT1.D on rat B lymphocytes: effects of interleukin-4, interleukin-13 and interferon-gamma

    NARCIS (Netherlands)

    Roos, A.; Schilder-Tol, E. J.; Chand, M. A.; Claessen, N.; Lakkis, F. G.; Pascual, D. W.; Weening, J. J.; Aten, J.

    1998-01-01

    Susceptibility to induction of both T helper 1- (Th1) and Th2-mediated autoimmunity is multifactorial and involves genetic linkage to the major histocompatibility complex (MHC) class II haplotype. Brown Norway (BN) rats exposed to mercuric chloride develop a Th2-dependent systemic autoimmunity,

  2. A novel and simple cell-based detection system with a collagen-encapsulated B-lymphocyte cell line as a biosensor for rapid detection of pathogens and toxins.

    Science.gov (United States)

    Banerjee, Pratik; Lenz, Dominik; Robinson, Joseph Paul; Rickus, Jenna L; Bhunia, Arun K

    2008-02-01

    Cell-based biosensors (CBBs) are becoming important tools for biosecurity applications and rapid diagnostics in food microbiology for their unique capability of detecting physiologically hazardous materials. A multi-well plate-based biosensor containing B-cell hybridoma, Ped-2E9, encapsulated in type I collagen matrix, was developed for rapid detection of viable cells of pathogenic Listeria, the toxin listeriolysin O, and the enterotoxin from Bacillus species. This sensor measures the alkaline phosphatase release from infected Ped-2E9 cells colorimetrically. Pathogenic L. monocytogenes cells and toxin preparations from L. monocytogenes or B. cereus showed cytotoxicity ranging from 24 to 98% at 3-6 h postinfection. In contrast, nonpathogenic L. innocua (F4247) and B. subtilis induced minimal cytotoxicity, ranging only 0.4-7.6%. Laser scanning cytometry and cryo-nano scanning electron microscopy confirmed the live or dead status of the infected Ped-2E9 cells in gel matrix. This paper presents the first example of a cell-based sensing system using collagen-encapsulated mammalian cells for rapid detection of pathogenic bacteria or toxin, and demonstrates a potential for onsite use as a portable detection system.

  3. Effects of belimumab, a B lymphocyte stimulator-specific inhibitor, on disease activity across multiple organ domains in patients with systemic lupus erythematosus: combined results from two phase III trials

    Science.gov (United States)

    Manzi, Susan; Sánchez-Guerrero, Jorge; Merrill, Joan T; Furie, Richard; Gladman, Dafna; Navarra, Sandra V; Ginzler, Ellen M; D'Cruz, David P; Doria, Andrea; Cooper, Simon; Zhong, Z John; Hough, Douglas; Freimuth, William; Petri, Michelle A

    2012-01-01

    Objective To evaluate the effects of belimumab versus placebo, plus standard systemic lupus erythematosus (SLE) therapy, on organ domain-specific SLE disease activity. Methods Data obtained after 52 weeks of treatment from two phase III trials (BLISS-52 and BLISS-76) comparing belimumab 1 and 10 mg/kg versus placebo, plus standard therapy, in 1684 autoantibody-positive patients were analysed post hoc for changes in British Isles Lupus Assessment Group (BILAG) and Safety of Estrogens in Lupus National Assessment–Systemic Lupus Erythematosus Disease Activity Index (SELENA–SLEDAI) organ domain scores. Results At baseline, the domains involved in the majority of patients were musculoskeletal and mucocutaneous by both BILAG and SELENA–SLEDAI, and immunological by SELENA–SLEDAI. At 52 weeks, significantly more patients treated with belimumab versus placebo had improvement in BILAG musculoskeletal and mucocutaneous domains (1 and 10 mg/kg), and in SELENA–SLEDAI mucocutaneous (10 mg/kg), musculoskeletal (1 mg/kg) and immunological (1 and 10 mg/kg) domains. Improvement was also observed in other organ systems with a low prevalence (≤16%) at baseline, including the SELENA–SLEDAI vasculitis and central nervous system domains. Significantly fewer patients treated with belimumab versus placebo had worsening in the BILAG haematological domain (1 mg/kg) and in the SELENA–SLEDAI immunological (10 mg/kg), haematological (10 mg/kg) and renal (1 mg/kg) domains. Conclusions Belimumab treatment improved overall SLE disease activity in the most common musculoskeletal and mucocutaneous organ domains. Less worsening occurred in the haematological, immunological and renal domains. PMID:22550315

  4. Sistema imunitário - parte II: fundamentos da resposta imunológica mediada por linfócitos T e B Immune system - part II: basis of the immunological response mediated by T and B lymphocytes

    Directory of Open Access Journals (Sweden)

    Danilo Mesquita Júnior

    2010-10-01

    Full Text Available O sistema imunológico é constituído por uma intrincada rede de órgãos, células e moléculas, e tem por finalidade manter a homeostase do organismo, combatendo as agressões em geral. A imunidade inata atua em conjunto com a imunidade adaptativa e caracteriza-se pela rápida resposta à agressão, independentemente de estímulo prévio, sendo a primeira linha de defesa do organismo. Seus mecanismos compreendem barreiras físicas, químicas e biológicas, componentes celulares e moléculas solúveis. A primeira defesa do organismo frente a um dano tecidual envolve diversas etapas intimamente integradas e constituídas pelos diferentes componentes desse sistema. A presente revisão tem como objetivo resgatar os fundamentos dessa resposta, que apresenta elevada complexidade e é constituída por diversos componentes articulados que convergem para a elaboração da resposta imune adaptativa. Destacamos algumas etapas: reconhecimento molecular dos agentes agressores; ativação de vias bioquímicas intracelulares que resultam em modificações vasculares e teciduais; produção de uma miríade de mediadores com efeitos locais e sistêmicos no âmbito da ativação e proliferação celulares, síntese de novos produtos envolvidos na quimioatração e migração de células especializadas na destruição e remoção do agente agressor, e finalmente a recuperação tecidual com o restabelecimento funcional do tecido ou órgão.The immune system consists of an intricate network of organs, cells, and molecules responsible for maintaining the body's homeostasis and responding to aggression in general. Innate immunity operates in conjunction with adaptive immunity and is characterized by rapid response to aggression, regardless of previous stimulus, being the organism first line of defense. Its mechanisms include physical, chemical and biological barriers, cellular components, as well as soluble molecules. The organism first line of defense against tissue damage involves several steps closely integrated and constituted by different components of this system. The aim of this review is to restore the foundations of this response, which has high complexity and consists of several components that converge to articulate the development of adaptive immune response. We selected some of the following steps to review: perception and molecular recognition of aggressive agents; activation of intracellular pathways, which result in vascular and tissue changes; production of a myriad of mediators with local and systemic effects on cell activation and proliferation, synthesis of new products involved in the chemoattraction and migration of cells specialized in destruction and removal of offending agent; and finally, tissue recovery with restoration of functional tissue or organ.

  5. Experiment list: SRX193598 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ription=B-lymphocyte, lymphoblastoid, International HapMap Project, CEPH/Utah pedigree 1459, treatment: Epst...2865 || cell organism=human || cell description=B-lymphocyte, lymphoblastoid, International HapMap Project,

  6. Experiment list: SRX150467 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available erm|Description=B-lymphocyte, lymphoblastoid, International HapMap Project, CEPH/Utah pedigree 1463, treatme...l=GM12891 || cell organism=human || cell description=B-lymphocyte, lymphoblastoid, International HapMap Project

  7. Experiment list: SRX102991 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available erm|Description=B-lymphocyte, lymphoblastoid, International HapMap Project - CEPH/Utah - European Caucasion,...Sequencing || cell description=B-lymphocyte, lymphoblastoid, International HapMap Project - CEPH/Utah - Euro

  8. Experiment list: SRX100534 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ription=B-lymphocyte, lymphoblastoid, International HapMap Project, CEPH/Utah pedigree 1463, treatment: Epst...description=Chromatin IP Sequencing || cell description=B-lymphocyte, lymphoblastoid, International HapMap Project

  9. Experiment list: SRX100522 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available iption=B-lymphocyte, lymphoblastoid, International HapMap Project - CEPH/Utah - European Caucasion, Epstein-...on=B-lymphocyte, lymphoblastoid, International HapMap Project - CEPH/Utah - European Caucasion, Epstein-Barr

  10. Experiment list: SRX100443 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ription=B-lymphocyte, lymphoblastoid, International HapMap Project, CEPH/Utah pedigree 1463, treatment: Epst...cription=Chromatin IP Sequencing || cell description=B-lymphocyte, lymphoblastoid, International HapMap Project

  11. Experiment list: SRX150466 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available mesoderm|Description=B-lymphocyte, lymphoblastoid, International HapMap Project - CEPH/Utah - European Cauca...ription=B-lymphocyte, lymphoblastoid, International HapMap Project - CEPH/Utah -

  12. Experiment list: SRX100582 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ription=B-lymphocyte, lymphoblastoid, International HapMap Project - CEPH/Utah - European Caucasion, Epstein...=B-lymphocyte, lymphoblastoid, International HapMap Project - CEPH/Utah - European Caucasion, Epstein-Barr V

  13. Experiment list: SRX100391 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available erm|Description=B-lymphocyte, lymphoblastoid, International HapMap Project - CEPH/Utah - European Caucasion,... description=Chromatin IP Sequencing || cell description=B-lymphocyte, lymphoblastoid, International HapMap Project

  14. Experiment list: SRX150365 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ription=B-lymphocyte, lymphoblastoid, International HapMap Project, CEPH/Utah pedigree 1463, treatment: Epst...GM12892 || cell organism=human || cell description=B-lymphocyte, lymphoblastoid, International HapMap Project

  15. Experiment list: SRX150367 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available mesoderm|Description=B-lymphocyte, lymphoblastoid, International HapMap Project, CEPH/Utah pedigree 1463, tr... || cell=GM12891 || cell organism=human || cell description=B-lymphocyte, lymphoblastoid, International HapMap Project

  16. Experiment list: SRX150529 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available erm|Description=B-lymphocyte, lymphoblastoid, International HapMap Project - CEPH/Utah - European Caucasion,...ell organism=human || cell description=B-lymphocyte, lymphoblastoid, International HapMap Project - CEPH/Uta

  17. Experiment list: SRX100400 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available mesoderm|Description=B-lymphocyte, lymphoblastoid, International HapMap Project - CEPH/Utah - European Cauca...ll description=B-lymphocyte, lymphoblastoid, International HapMap Project - CEPH/Utah - European Caucasion,

  18. Experiment list: SRX150605 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ription=B-lymphocyte, lymphoblastoid, International HapMap Project, CEPH/Utah pedigree 1463, treatment: Epst...GM12891 || cell organism=human || cell description=B-lymphocyte, lymphoblastoid, International HapMap Project

  19. Experiment list: SRX111778 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ription=B-lymphocyte, lymphoblastoid, International HapMap Project, CEPH/Utah pedigree 1459, treatment: Epst...nism=human || cell description=B-lymphocyte, lymphoblastoid, International HapMap Project, CEPH/Utah pedigre

  20. Experiment list: SRX150719 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available mesoderm|Description=B-lymphocyte, lymphoblastoid, International HapMap Project, CEPH/Utah pedigree 1463, tr... || cell=GM12892 || cell organism=human || cell description=B-lymphocyte, lymphoblastoid, International HapMap Project

  1. Experiment list: SRX190043 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available erm|Description=B-lymphocyte, lymphoblastoid, International HapMap Project, CEPH/Utah pedigree 1459, treatme...ll description=B-lymphocyte, lymphoblastoid, International HapMap Project, CEPH/U

  2. Experiment list: SRX067503 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ription=B-lymphocyte, lymphoblastoid, International HapMap Project - CEPH/Utah - European Caucasion, Epstein...=Chromatin IP Sequencing || cell organism=human || cell description=B-lymphocyte, lymphoblastoid, International HapMap Project

  3. Experiment list: SRX190078 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ion=B-lymphocyte, lymphoblastoid, International HapMap Project, CEPH/Utah pedigree 1459, treatment: Epstein-...iption=B-lymphocyte, lymphoblastoid, International HapMap Project, CEPH/Utah pedi

  4. Experiment list: SRX190017 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available erm|Description=B-lymphocyte, lymphoblastoid, International HapMap Project, CEPH/Utah pedigree 1459, treatme...l description=B-lymphocyte, lymphoblastoid, International HapMap Project, CEPH/Ut

  5. Experiment list: SRX199857 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ription=B-lymphocyte, lymphoblastoid, International HapMap Project, CEPH/Utah pedigree 1459, treatment: Epst...M12873 || cell organism=human || cell description=B-lymphocyte, lymphoblastoid, International HapMap Project

  6. Experiment list: SRX111775 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ription=B-lymphocyte, lymphoblastoid, International HapMap Project, CEPH/Utah pedigree 1459, treatment: Epst...ism=human || cell description=B-lymphocyte, lymphoblastoid, International HapMap Project, CEPH/Utah pedigree

  7. Experiment list: SRX150557 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ription=B-lymphocyte, lymphoblastoid, International HapMap Project - CEPH/Utah - European Caucasion, Epstein... organism=human || cell description=B-lymphocyte, lymphoblastoid, International HapMap Project - CEPH/Utah -

  8. Experiment list: SRX190003 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ion=B-lymphocyte, lymphoblastoid, International HapMap Project, CEPH/Utah pedigree 1459, treatment: Epstein-...ription=B-lymphocyte, lymphoblastoid, International HapMap Project, CEPH/Utah ped

  9. Experiment list: SRX100444 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available mesoderm|Description=B-lymphocyte, lymphoblastoid, International HapMap Project, CEPH/Utah pedigree 1463, tr...datatype description=Chromatin IP Sequencing || cell description=B-lymphocyte, lymphoblastoid, International HapMap Project

  10. Experiment list: SRX100396 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available erm|Description=B-lymphocyte, lymphoblastoid, International HapMap Project - CEPH/Utah - European Caucasion,...pe description=Chromatin IP Sequencing || cell description=B-lymphocyte, lymphoblastoid, International HapMap Project

  11. Experiment list: SRX100526 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available erm|Description=B-lymphocyte, lymphoblastoid, International HapMap Project, CEPH/Utah pedigree 1463, treatme...eq || datatype description=Chromatin IP Sequencing || cell description=B-lymphocyte, lymphoblastoid, International HapMap Project

  12. Experiment list: SRX199864 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ription=B-lymphocyte, lymphoblastoid, International HapMap Project, CEPH/Utah pedigree 1459, treatment: Epst...12865 || cell organism=human || cell description=B-lymphocyte, lymphoblastoid, International HapMap Project,

  13. Experiment list: SRX150643 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available erm|Description=B-lymphocyte, lymphoblastoid, International HapMap Project - CEPH/Utah - European Caucasion,...|| cell organism=human || cell description=B-lymphocyte, lymphoblastoid, International HapMap Project - CEPH

  14. Experiment list: SRX100431 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ription=B-lymphocyte, lymphoblastoid, International HapMap Project - CEPH/Utah - European Caucasion, Epstein... description=B-lymphocyte, lymphoblastoid, International HapMap Project - CEPH/Utah - European Caucasion, Ep

  15. Experiment list: SRX150366 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available erm|Description=B-lymphocyte, lymphoblastoid, International HapMap Project, CEPH/Utah pedigree 1463, treatme...l=GM12892 || cell organism=human || cell description=B-lymphocyte, lymphoblastoid, International HapMap Project

  16. Experiment list: SRX067493 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available erm|Description=B-lymphocyte, lymphoblastoid, International HapMap Project - CEPH/Utah - European Caucasion,...tion=B-lymphocyte, lymphoblastoid, International HapMap Project - CEPH/Utah - European Caucasion, Epstein-Ba

  17. Experiment list: SRX100530 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available mesoderm|Description=B-lymphocyte, lymphoblastoid, International HapMap Project - CEPH/Utah - European Cauca... cell description=B-lymphocyte, lymphoblastoid, International HapMap Project - CEPH/Utah - European Caucasio

  18. Experiment list: SRX067518 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available n=B-lymphocyte, lymphoblastoid, International HapMap Project - CEPH/Utah - European Caucasion, Epstein-Barr ...atin IP Sequencing || cell organism=human || cell description=B-lymphocyte, lymphoblastoid, International HapMap Project

  19. Experiment list: SRX190021 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available erm|Description=B-lymphocyte, lymphoblastoid, International HapMap Project, CEPH/Utah pedigree 1459, treatme...l description=B-lymphocyte, lymphoblastoid, International HapMap Project, CEPH/Ut

  20. Experiment list: SRX067509 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available tion=B-lymphocyte, lymphoblastoid, International HapMap Project - CEPH/Utah - European Caucasion, Epstein-Ba...Chromatin IP Sequencing || cell organism=human || cell description=B-lymphocyte, lymphoblastoid, International HapMap Project

  1. Experiment list: SRX111774 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ription=B-lymphocyte, lymphoblastoid, International HapMap Project, CEPH/Utah pedigree 1459, treatment: Epst...nism=human || cell description=B-lymphocyte, lymphoblastoid, International HapMap Project, CEPH/Utah pedigre

  2. Experiment list: SRX100909 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ription=B-lymphocyte, lymphoblastoid, International HapMap Project, CEPH/Utah pedigree 1463, treatment: Epst...equencing || cell description=B-lymphocyte, lymphoblastoid, International HapMap Project, CEPH/Utah pedigree...ll description=B-Lymphocyte, Lymphoblastoid, International HapMap Project, CEPH/Utah pedigree 1463, Treatmen

  3. Experiment list: SRX100908 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ription=B-lymphocyte, lymphoblastoid, International HapMap Project, CEPH/Utah pedigree 1463, treatment: Epst...equencing || cell description=B-lymphocyte, lymphoblastoid, International HapMap Project, CEPH/Utah pedigree...escription=B-Lymphocyte, Lymphoblastoid, International HapMap Project, CEPH/Utah pedigree 1463, Treatment: E

  4. Experiment list: SRX100911 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ription=B-lymphocyte, lymphoblastoid, International HapMap Project, Yoruba in Ibadan, Nigera, treatment: Eps...Sequencing || cell description=B-lymphocyte, lymphoblastoid, International HapMap Project, Yoruba in Ibadan,... description=B-Lymphocyte, Lymphoblastoid, International HapMap Project, Yoruba in Ibadan, Nigera, Treatment

  5. Experiment list: SRX100910 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ription=B-lymphocyte, lymphoblastoid, International HapMap Project, Yoruba in Ibadan, Nigera, treatment: Eps...Sequencing || cell description=B-lymphocyte, lymphoblastoid, International HapMap Project, Yoruba in Ibadan,...cell description=B-Lymphocyte, Lymphoblastoid, International HapMap Project, Yoruba in Ibadan, Nigera, Treat

  6. Experiment list: SRX100903 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ription=B-lymphocyte, lymphoblastoid, International HapMap Project, Yoruba in Ibadan, Nigera, treatment: Eps... HS Sequencing || cell description=B-lymphocyte, lymphoblastoid, International HapMap Project, Yoruba in Iba... || cell description=B-Lymphocyte, Lymphoblastoid, International HapMap Project, Yoruba in Ibadan, Nigera, T

  7. Effects of spaceflight on the immunoglobulin repertoire of unimmunized C57BL/6 mice

    Data.gov (United States)

    National Aeronautics and Space Administration — Spaceflight has been shown to suppress the adaptive immune response altering the distribution and function of lymphocyte populations. B lymphocytes express highly...

  8. Experiment list: SRX080425 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ription=B-lymphocyte, lymphoblastoid, International HapMap Project, CEPH/Utah pedigree 1459, treatment: Epst....aspx?Ref=GM12864 || cell=GM12864 || cell organism=Human || cell description=B-Lymphocyte, Lymphoblastoid, International HapMap Proje...ct, CEPH/Utah pedigree 1459, Treatment: Epstein-Barr Virus transformed || cell kary

  9. Experiment list: SRX080393 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ription=B-lymphocyte, lymphoblastoid, International HapMap Project, CEPH/Utah pedigree 1459, treatment: Epst...aspx?Ref=GM12873 || cell=GM12873 || cell organism=Human || cell description=B-Lymphocyte, Lymphoblastoid, International HapMap Projec

  10. The two faces of endogenous DNA editing enzymes: Promoting ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Type B lymphocytes are a specific type of white blood cell within our immune system. They produce and export antibodies which seek out, attach to, and neutralize microbes and toxins. A unique way that B lymphocytes boost their antibody response is through making changes in the genes that encode for antibodies.

  11. XLA patients with BTK splice-site mutations produce low levels of wild-type BTK transcripts.

    NARCIS (Netherlands)

    Noordzij, J.G.; Bruin-Versteeg, S. de; Hartwig, N.G.; Weemaes, C.M.R.; Gerritsen, E.J.; Bernatowska, E.; Lierde, S. van; Groot, R. de; Dongen, J.J.M. van

    2002-01-01

    X-linked agammaglobulinemia is caused by mutations in the BTK gene, which result in a precursor B-cell differentiation arrest in the bone marrow and the absence of or strongly reduced B lymphocytes in blood. We identified a patient with a mild clinical phenotype, low numbers of B lymphocytes, and a

  12. Experiment list: SRX069154 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ription=B-lymphocyte, lymphoblastoid, International HapMap Project, CEPH/Utah pedigree 1459, treatment: Epst...&q=GM12865 || cell=GM12865 || cell organism=Human || cell description=B-Lymphocyte, Lymphoblastoid, International HapMap Project

  13. Experiment list: SRX080333 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ription=B-lymphocyte, lymphoblastoid, International HapMap Project, CEPH/Utah pedigree 1459, treatment: Epst....aspx?Ref=GM12875 || cell=GM12875 || cell organism=Human || cell description=B-Lymphocyte, Lymphoblastoid, International HapMap Proje...ct, CEPH/Utah pedigree 1459, Treatment: Epstein-Barr Virus transformed || cell kary

  14. Experiment list: SRX100527 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available erm|Description=B-lymphocyte, lymphoblastoid, International HapMap Project, CEPH/Utah pedigree 1463, treatme...ChipSeq || datatype description=Chromatin IP Sequencing || cell description=B-lymphocyte, lymphoblastoid, International HapMap Projec..., Lymphoblastoid, International HapMap Project, CEPH/Utah pedigree 1463, Treatment: Epstein-Barr Virus trans

  15. Experiment list: SRX100458 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available erm|Description=B-lymphocyte, lymphoblastoid, International HapMap Project - CEPH/Utah - European Caucasion,...ype description=Chromatin IP Sequencing || cell description=B-lymphocyte, lymphoblastoid, International HapMap Project...ll organism=human || cell description=lymphoblastoid, International HapMap Project

  16. Experiment list: SRX080364 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available erm|Description=B-lymphocyte, lymphoblastoid, International HapMap Project, CEPH/Utah, treatment: Epstein-Ba...f=GM12801 || cell=GM12801 || cell organism=Human || cell description=B-Lymphocyte, Lymphoblastoid, International HapMap Project

  17. Experiment list: SRX080339 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ription=B-lymphocyte, lymphoblastoid, International HapMap Project, CEPH/Utah pedigree 1459, treatment: Epst...aspx?Ref=GM12864 || cell=GM12864 || cell organism=Human || cell description=B-Lymphocyte, Lymphoblastoid, International HapMap Projec

  18. Experiment list: SRX100533 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available erm|Description=B-lymphocyte, lymphoblastoid, International HapMap Project, CEPH/Utah pedigree 1463, treatme...hipSeq || datatype description=Chromatin IP Sequencing || cell description=B-lymphocyte, lymphoblastoid, International HapMap Project...ymphoblastoid, International HapMap Project, CEPH/Utah pedigree 1463, Treatment: Epstein-Barr Virus transfor

  19. Experiment list: SRX069105 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ription=B-lymphocyte, lymphoblastoid, International HapMap Project, CEPH/Utah pedigree 1459, treatment: Epst...&q=GM12865 || cell=GM12865 || cell organism=Human || cell description=B-Lymphocyte, Lymphoblastoid, International HapMap Project

  20. Experiment list: SRX069118 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ription=B-lymphocyte, lymphoblastoid, International HapMap Project, CEPH/Utah pedigree 1459, treatment: Epst...&q=GM12864 || cell=GM12864 || cell organism=Human || cell description=B-Lymphocyte, Lymphoblastoid, International HapMap Project

  1. Experiment list: SRX080403 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ription=B-lymphocyte, lymphoblastoid, International HapMap Project, CEPH/Utah pedigree 1459, treatment: Epst....aspx?Ref=GM12865 || cell=GM12865 || cell organism=Human || cell description=B-Lymphocyte, Lymphoblastoid, International HapMap Proje...ct, CEPH/Utah pedigree 1459, Treatment: Epstein-Barr Virus transformed || cell kary

  2. Experiment list: SRX100512 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available erm|Description=B-lymphocyte, lymphoblastoid, International HapMap Project, CEPH/Utah pedigree 1463, treatme...hipSeq || datatype description=Chromatin IP Sequencing || cell description=B-lymphocyte, lymphoblastoid, International HapMap Project... Lymphoblastoid, International HapMap Project, CEPH/Utah pedigree 1463, Treatment: Epstein-Barr Virus transf

  3. Experiment list: SRX080355 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ription=B-lymphocyte, lymphoblastoid, International HapMap Project, CEPH/Utah pedigree 1459, treatment: Epst....aspx?Ref=GM12872 || cell=GM12872 || cell organism=Human || cell description=B-Lymphocyte, Lymphoblastoid, International HapMap Proje...ct, CEPH/Utah pedigree 1459, Treatment: Epstein-Barr Virus transformed || cell kary

  4. Experiment list: SRX100481 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available erm|Description=B-lymphocyte, lymphoblastoid, International HapMap Project - CEPH/Utah - European Caucasion,...type description=Chromatin IP Sequencing || cell description=B-lymphocyte, lymphoblastoid, International HapMap Project...ell organism=human || cell description=lymphoblastoid, International HapMap Project

  5. What we do | Page 7 | IDRC - International Development Research ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    The two faces of endogenous DNA editing enzymes: Promoting gene mutations as well as genome repair. Type B lymphocytes are a specific type of white blood cell within our immune system. Global. PROJECT ...

  6. Medline Plus

    Full Text Available ... the bone marrow, B cells migrate through the body fluids to the lymph nodes, spleen and blood. B lymphocytes provide the body with humoral immunity as they circulate in the ...

  7. Experiment list: SRX150586 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ription=B-lymphocyte, lymphoblastoid, International HapMap Project - CEPH/Utah - European Caucasion, Epstein...ocyte, lymphoblastoid, International HapMap Project - CEPH/Utah - European Caucas

  8. Experiment list: SRX150412 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available cription=B-lymphocyte, lymphoblastoid, International HapMap Project - CEPH/Utah - European Caucasion, Epstei...mphocyte, lymphoblastoid, International HapMap Project - CEPH/Utah - European Cau

  9. Medline Plus

    Full Text Available ... immunity becomes deficient in persons with HIV, the virus that causes AIDS, because HIV attacks and destroys helper T cells. The other group of lymphocytes, B lymphocytes or B cells, mature and develop within ...

  10. Medline Plus

    Full Text Available ... helper T cells. The other group of lymphocytes, B lymphocytes or B cells, mature and develop within the bone marrow ... recognize specific foreign invaders. From the bone marrow, B cells migrate through the body fluids to the ...

  11. What we do | Page 14 | IDRC - International Development Research ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    The two faces of endogenous DNA editing enzymes: Promoting gene mutations as well as genome repair. Type B lymphocytes are a specific type of white blood cell within our immune system. Canada, Israel. PROJECT ...

  12. What we do | Page 7 | IDRC - International Development Research ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    The two faces of endogenous DNA editing enzymes: Promoting gene mutations as well as genome repair. Type B lymphocytes are a specific type of white blood cell within our immune system. India, Pakistan, Canada, Israel. PROJECT ...

  13. Experiment list: SRX208212 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available id cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of...SRX208212 mm9 Unclassified Unclassified Blood B-Lymphocytes MeSH Description=Lympho

  14. Experiment list: SRX208218 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available id cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of...SRX208218 mm9 Unclassified Unclassified Blood B-Lymphocytes MeSH Description=Lympho

  15. B-Cell Metabolic Remodeling and Cancer

    DEFF Research Database (Denmark)

    Franchina, Davide G.; Grusdat, Melanie; Brenner, Dirk

    2018-01-01

    Cells of the immune system display varying metabolic profiles to fulfill their functions. B lymphocytes overcome fluctuating energy challenges as they transition from the resting state and recirculation to activation, rapid proliferation, and massive antibody production. Only through a controlled...

  16. Experiment list: SRX069089 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ription=B-lymphocyte, lymphoblastoid, International HapMap Project - CEPH/Utah - European Caucasion, Epstein...| cell lineage=International HapMap Project - CEPH/Utah - European Caucasion; Epstein-Barr Virus || cell sex

  17. Experiment list: SRX080348 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available erm|Description=B-lymphocyte, lymphoblastoid, International HapMap Project, CEPH/Utah pedigree 1459, treatme...oid, International HapMap Project, CEPH/Utah pedigree 1459, Treatment: Epstein-Barr Virus transformed || cel

  18. Experiment list: SRX080417 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available erm|Description=B-lymphocyte, lymphoblastoid, International HapMap Project, CEPH/Utah pedigree 1459, treatme...oid, International HapMap Project, CEPH/Utah pedigree 1459, Treatment: Epstein-Barr Virus transformed || cel

  19. Experiment list: SRX189971 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ion=B-lymphocyte, lymphoblastoid, International HapMap Project - CEPH/Utah - European Caucasion, Epstein-Bar...cyte, lymphoblastoid, International HapMap Project - CEPH/Utah - European Caucasi

  20. Experiment list: SRX069228 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ription=B-lymphocyte, lymphoblastoid, International HapMap Project, CEPH/Utah, treatment: Epstein-Barr Virus... cell=GM06990 || cell organism=Human || cell description=Lymphoblastoid, International HapMap Project, CEPH/

  1. Experiment list: SRX150489 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available iption=B-lymphocyte, lymphoblastoid, International HapMap Project - CEPH/Utah - European Caucasion, Epstein-...stoid, International HapMap Project - CEPH/Utah - European Caucasion, Epstein-Bar

  2. Experiment list: SRX069151 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ription=B-lymphocyte, lymphoblastoid, International HapMap Project, CEPH/Utah, treatment: Epstein-Barr Virus... cell=GM06990 || cell organism=Human || cell description=Lymphoblastoid, International HapMap Project, CEPH/

  3. Experiment list: SRX080332 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available erm|Description=B-lymphocyte, lymphoblastoid, International HapMap Project - CEPH/Utah - European Caucasion,...f=GM12878 || cell=GM12878 || cell organism=Human || cell description=lymphoblastoid, International HapMap Project

  4. Experiment list: SRX189962 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ion=B-lymphocyte, lymphoblastoid, International HapMap Project, CEPH/Utah, treatment: Epstein-Barr Virus tra...ocyte, lymphoblastoid, International HapMap Project, CEPH/Utah, treatment: Epstei

  5. Experiment list: SRX080440 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available erm|Description=B-lymphocyte, lymphoblastoid, International HapMap Project, CEPH/Utah pedigree 1459, treatme...oid, International HapMap Project, CEPH/Utah pedigree 1459, Treatment: Epstein-Barr Virus transformed || cel

  6. Experiment list: SRX080371 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ription=B-lymphocyte, lymphoblastoid, International HapMap Project, CEPH/Utah, treatment: Epstein-Barr Virus...90 || cell=GM06990 || cell organism=Human || cell description=Lymphoblastoid, International HapMap Project,

  7. Experiment list: SRX080405 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available erm|Description=B-lymphocyte, lymphoblastoid, International HapMap Project, CEPH/Utah pedigree 1459, treatme...oid, International HapMap Project, CEPH/Utah pedigree 1459, Treatment: Epstein-Barr Virus transformed || cel

  8. Experiment list: SRX080428 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available erm|Description=B-lymphocyte, lymphoblastoid, International HapMap Project, CEPH/Utah pedigree 1459, treatme...oid, International HapMap Project, CEPH/Utah pedigree 1459, Treatment: Epstein-Barr Virus transformed || cel

  9. Experiment list: SRX186608 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available scription=B-lymphocyte, lymphoblastoid, International HapMap Project - CEPH/Utah - European Caucasion, Epste...-lymphocyte, lymphoblastoid, International HapMap Project - CEPH/Utah - European

  10. Experiment list: SRX080368 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ription=B-lymphocyte, lymphoblastoid, International HapMap Project, CEPH/Utah, treatment: Epstein-Barr Virus...90 || cell=GM06990 || cell organism=Human || cell description=Lymphoblastoid, International HapMap Project,

  11. Experiment list: SRX080387 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available erm|Description=B-lymphocyte, lymphoblastoid, International HapMap Project, CEPH/Utah pedigree 1459, treatme...toid, International HapMap Project, CEPH/Utah pedigree 1459, Treatment: Epstein-Barr Virus transformed || ce

  12. Experiment list: SRX069213 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ription=B-lymphocyte, lymphoblastoid, International HapMap Project - CEPH/Utah - European Caucasion, Epstein...|| cell lineage=International HapMap Project - CEPH/Utah - European Caucasion; Epstein-Barr Virus || cell se

  13. B-lymfocytdepletring og andre biologiske behandlingsmuligheder ved Graves' oftalmopatiTumor necrosis factor-alpha binding capacity and anti-infliximab antibodies measured by fluid-phase radioimmunoassays as predictors of clinical efficacy of infliximab in Crohn's disease

    DEFF Research Database (Denmark)

    El, Fassi D.; Hegedus, L.; Nielsen, Claus Henrik

    2008-01-01

    The current medical treatment options for Graves' ophthalmopathy (GO) are unsatisfactory. Recent treatment of GO patients with the B-lymphocyte depleting monoclonal antibody rituximab or with the anti-tumor necrosis factor-alpha agents etanercept and infliximab has shown promising results. We...... discuss the use of these and other biological agents targeting B lymphocytes, T-lymphocyte interaction with antigen-presenting cells, or cytokines in the future treatment of GO Udgivelsesdato: 2008/6/9...

  14. Biologiske behandlingsmuligheder ved Graves' oftalmopati

    DEFF Research Database (Denmark)

    El Fassi, Daniel; Nielsen, Claus; Hegedüs, Laszlo

    2008-01-01

    The current medical treatment options for Graves' ophthalmopathy (GO) are unsatisfactory. Recent treatment of GO patients with the B-lymphocyte depleting monoclonal antibody rituximab or with the anti-tumor necrosis factor-alpha agents etanercept and infliximab has shown promising results. We...... discuss the use of these and other biological agents targeting B lymphocytes, T-lymphocyte interaction with antigen-presenting cells, or cytokines in the future treatment of GO....

  15. Space Flight-Induced Reactivation of Latent Epstein-Barr Virus

    Science.gov (United States)

    Stowe, Raymond P.; Barrett, Alan D. T.; Pierson, Duane L.

    2001-01-01

    Reactivation of latent Epstein-Barr virus (EBV) may be an important threat to crew health during extended space missions. Decreased cellular immune function has been reported both during and after space flight. Preliminary studies have demonstrated increased EBV shedding in saliva as well as increased antibody titers to EBV lytic proteins. We hypothesize that the combined effects of microgravity along with associated physical and psychological stress will decrease EBV-specific T-cell immunity and reactivate latent EBV in infected B-lymphocytes. If increased virus production and clonal expansion of infected B-lymphocytes are detected, then pharmacological measures can be developed and instituted prior to onset of overt clinical disease. More importantly, we will begin to understand the basic mechanisms involved in stress-induced reactivation of EBV in circulating B-lymphocytes.

  16. Effect of UV radiation on the surface of mammalian immunocompetent cells. 1. The change in expression of some antigens and receptors of murine spleen lymphocyte surface

    Energy Technology Data Exchange (ETDEWEB)

    Krylenkov, V.A.; Malygin, A.M. (AN SSSR, Leningrad. Inst. Tsitologii)

    1982-12-01

    Short-wave (254nm) and long-wave (365 nm) UV rays (ShUS and LUV rays) induce the increase in the expression of surface markers of T lymphocytes-THETA(Thy-1) antigens and B lymphocytes-MBLA-antigens and EAS receptors when affecting mouse spleen cells in nonlethal and small lethal doses. Total cell content with T and B lymphocyte characters in an irradiated suspension exceeds even the total cell quantity in non-irradiated suspension (100%) which points to the possibility of the expression of plasmatic membrane antigens and receptors not manifested on the surface of nonirradiated lymphocytes. In the isolethal dose range (LD/sup 15/-LD/sup 28/) ShUV rays suppress and LUV rays induce further increase of THETA and MBLA antigens expression. Among B lymphocytes surface markers the MBLA antigens are more resistant to ShUV an LUV radiation as compared with the EAC receptors.

  17. Small lymphocytes in peripheral lymphoid tissues of nude mice. Life-span and distribution

    DEFF Research Database (Denmark)

    Hougen, H P; Röpke, C

    1975-01-01

    The distribution of small lymphocytes according to life-span in the peripheral lymphoid tissues of the mouse mutant "nude" has been studied by means of auto-radiography and scintillation counting to evaluate the localization of B lymphocytes with varying life-span. The vast majority of the lympho......The distribution of small lymphocytes according to life-span in the peripheral lymphoid tissues of the mouse mutant "nude" has been studied by means of auto-radiography and scintillation counting to evaluate the localization of B lymphocytes with varying life-span. The vast majority...

  18. Proliferation and performance of hybridoma cells in microgravity (7-IML-1)

    Science.gov (United States)

    Cogoli, Augusto

    1992-01-01

    The purpose of this experiment is to study how cell performance (biosynthesis and secretion) is altered by altered gravity conditions. Hybridoma cells are obtained by fusion of an activated B-lymphocyte with a myeloma cell. Activated B-lymphocytes, derived from a human or an animal, carry the information required to produce antibodies of a certain specificity and can survive only a few days in culture. Myeloma cells are tumor cells which can grow indefinitely in culture. Therefore, the product of the fusion is an immortal cell line capable of producing homogeneous antibodies (monoclonal antibodies). Experimental procedures are explained in some detail.

  19. B-lineage transcription factors and cooperating gene lesions required for leukemia development

    NARCIS (Netherlands)

    Tijchon, E.J.H.; Havinga, J.; Leeuwen, F.N. van; Scheijen, B.

    2013-01-01

    Differentiation of hematopoietic stem cells into B lymphocytes requires the concerted action of specific transcription factors, such as RUNX1, IKZF1, E2A, EBF1 and PAX5. As key determinants of normal B-cell development, B-lineage transcription factors are frequently deregulated in hematological

  20. Search Results | Page 35 | IDRC - International Development ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Results 341 - 350 of 8494 ... Type B lymphocytes are a specific type of white blood cell within our immune system. They produce and export antibodies which seek out, attach to, and neutralize microbes and toxins. Project. Epitope focused immunogens and recombinant antibody therapeutics for the control of tropical diseases.

  1. Profiling of polychromatic flow cytometry data on B-cells reveals patients' clusters in common variable immunodeficiency

    Czech Academy of Sciences Publication Activity Database

    Kalina, T.; Stuchlý, J.; Janda, A.; Hrušák, O.; Růžičková, Šárka; Šedivá, A.; Litzman, J.; Vlková, M.

    2009-01-01

    Roč. 75, č. 11 (2009), s. 902-909 ISSN 1552-4922 Institutional research plan: CEZ:AV0Z50520701 Keywords : binning * B lymphocyte profiling * common variable immunodeficiency Subject RIV: EC - Immunology Impact factor: 3.032, year: 2009

  2. Characterization of Lymphocyte Subsets in Patients with Common Variable Immunodeficiency Reveals Subsets of Naive Human B Cells Marked by CD24 Expression

    Czech Academy of Sciences Publication Activity Database

    Vlková, M.; Froňková, E.; Kanderová, V.; Janda, A.; Růžičková, Šárka; Litzman, J.; Šedivá, A.; Kalina, T.

    2010-01-01

    Roč. 185, č. 11 (2010), s. 6431-6438 ISSN 0022-1767 Institutional research plan: CEZ:AV0Z50520701 Keywords : B lymphocyte immunophenotyping * naive B cells * common variable immunodeficiency Subject RIV: EC - Immunology Impact factor: 5.745, year: 2010

  3. Wnt-expressing rat embryonic fibroblasts suppress Apo2L/TRAIL-induced apoptosis of human leukemia cells

    Czech Academy of Sciences Publication Activity Database

    Doubravská, Lenka; Šímová, Šárka; Čermák, Lukáš; Valenta, Tomáš; Kořínek, Vladimír; Anděra, Ladislav

    2008-01-01

    Roč. 13, č. 4 (2008), s. 573-587 ISSN 1360-8185 Institutional research plan: CEZ:AV0Z50520514 Keywords : Wnt * Apo2L/TRAIL * pre-B lymphocyte Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.971, year: 2008

  4. Requirement for CD40 ligand, CD4(+) T cells, and B cells in an infectious mononucleosis-like syndrome

    DEFF Research Database (Denmark)

    Brooks, J W; Hamilton-Easton, A M; Christensen, J P

    1999-01-01

    Respiratory challenge with the murine gammaherpesvirus 68 (gammaHV-68) results in productive infection of the lung, the establishment of latency in B lymphocytes and other cell types, transient splenomegaly, and prolonged clonal expansion of activated CD8(+) CD62L(lo) T cells, particularly a Vbeta4...

  5. Immune System

    Science.gov (United States)

    ... jobs to do: B lymphocytes are like the body's military intelligence system, seeking out their targets and sending defenses ... like the soldiers, destroying the invaders that the intelligence system has ... that invades the body is called an antigen (pronounced: AN-tih-jun). ...

  6. Search Results | Page 35 | IDRC - International Development ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Results 341 - 350 of 8491 ... The two faces of endogenous DNA editing enzymes: Promoting gene mutations as well as genome repair. Type B lymphocytes are a specific type of white blood cell within our immune system. They produce and export antibodies which seek out, attach to, and neutralize microbes and toxins.

  7. Search Results | Page 40 | IDRC - International Development ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Results 391 - 400 of 8492 ... The two faces of endogenous DNA editing enzymes: Promoting gene mutations as well as genome repair. Type B lymphocytes are a specific type of white blood cell within our immune system. They produce and export antibodies which seek out, attach to, and neutralize microbes and toxins.

  8. Characterization of cat dander-specific T lymphocytes from atopic patients

    NARCIS (Netherlands)

    van Neerven, R. J.; van de Pol, M. M.; van Milligen, F. J.; Jansen, H. M.; Aalberse, R. C.; Kapsenberg, M. L.

    1994-01-01

    Fel d I, the major cat dander allergen, is recognized by serum IgE of more than 80% of all cat-allergic patients. Because IgE synthesis by B lymphocytes is under the control of T lymphocytes, we studied the specificity and lymphokine production profiles of cat dander-specific T lymphocytes.

  9. Experimental Acanthamoeba keratitis: II. Immunohistochemical evaluation.

    Science.gov (United States)

    Larkin, D. F.; Easty, D. L.

    1991-01-01

    In a Wistar rat experimental model of Acanthamoeba keratitis immunohistochemical techniques were used to analyse the host cellular response. The inflammatory cell profile was observed to change at intervals. In tissue sections the cellular response consisted of neutrophils on the first day but predominantly macrophages on the following days. Some T lymphocytes but no B lymphocytes were observed. Images PMID:1854696

  10. T cell precursor migration towards beta 2-microglobulin is involved in thymus colonization of chicken embryos

    DEFF Research Database (Denmark)

    Dunon, D; Kaufman, J; Salomonsen, J

    1990-01-01

    isolated after migration towards beta 2m in vitro and shown to be able to colonize a 13 day old thymus in ovo, where they subsequently acquire thymocyte markers. In contrast these beta 2m responsive precursors did not colonize embryonic bursa, i.e. differentiate into B lymphocytes. During chicken...

  11. http://www.bioline.org.br/js 124 Ageing and its Effect on the ...

    African Journals Online (AJOL)

    jen

    H&E and immunostaining which contain antibodies to T and B lymphocytes were employed. Ethical review and approval of the study was sought from the faculty of medicine research and ethics committee which conducts reviews on behalf of the Uganda. National Council for Science and technology. Consent to dissect the ...

  12. The two faces of endogenous DNA editing enzymes: Promoting ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    The two faces of endogenous DNA editing enzymes: Promoting gene mutations as well as genome repair. Type B lymphocytes are a specific type of white blood cell within our immune system. They produce and export antibodies which seek out, attach to, and neutralize microbes and toxins. A unique way that B ...

  13. Is Tourette's syndrome an autoimmune disease?

    NARCIS (Netherlands)

    Hoekstra, PJ; Kallenberg, CGM; Korf, J; Minderaa, RB

    2002-01-01

    We provide a review of recent research findings which support the involvement of autoimmunity in childhood-onset tic disorders, in particular the presence of antineuronal autoantibodies, D8/17 B lymphocyte overexpression, a marker of chorea associated with streptococcal infection, and possible

  14. Chemokine stromal cell-derived factor 1alpha activates basophils by means of CXCR4

    DEFF Research Database (Denmark)

    Jinquan, T; Jacobi, H H; Jing, C

    2000-01-01

    The CXC chemokine receptor 4 (CXCR4) is predominantly expressed on inactivated naive T lymphocytes, B lymphocytes, dendritic cells, and endothelial cells. CXC chemokine stromal cell-derived factor 1alpha (SDF-1alpha) is the only known ligand for CXCR4. To date, the CXCR4 expression and function...... of SDF-1alpha in basophils are unknown....

  15. The enigma of the lower gut-associated lymphoid tissue (GALT)

    Czech Academy of Sciences Publication Activity Database

    Butler, J. E.; Šinkora, Marek

    2013-01-01

    Roč. 94, č. 2 (2013), s. 259-270 ISSN 0741-5400 R&D Projects: GA ČR GAP502/10/0038; GA ČR GAP502/12/0110 Institutional support: RVO:61388971 Keywords : B lymphocytes * lymphogenesis * B cell development Subject RIV: EC - Immunology Impact factor: 4.304, year: 2013

  16. Cationic liposomal drug delivery system for specific targeting of human cd14+ monocytes in whole blood

    DEFF Research Database (Denmark)

    2013-01-01

    blood when compared to adherence to granulocytes, T-lymphocytes, B- lymphocytes and/or NK cells in freshly drawn blood, to a lipid-based pharmaceutical composition comprising said liposomes and their use in monocytic associated prophylaxis, treatment or amelioration of a condition such as cancer...

  17. Blockade of Ca2+-activated K+ channels in T cells: an option for the treatment of multiple sclerosis?

    DEFF Research Database (Denmark)

    Madsen, Lars Siim; Christophersen, Palle; Olesen, Søren-Peter

    2005-01-01

    Voltage- and Ca(2+)-dependent K(+) channels in the membrane of both T and B lymphocytes are important for the cellular immune response. In the current issue of the European Journal of Immunology, Reich et al. demonstrate that selective blockade of the intermediate-conductance Ca(2+)-activated K(+...... of new immune-suppressant drugs for the treatment of autoimmune diseases....

  18. Passenger Lymphocyte Syndrome (PLS): A Single-center Retrospective Analysis of Minor ABO-incompatible Liver Transplants

    NARCIS (Netherlands)

    Bruijn, S. de; Philipse, E.; Couttenye, M.M.; Bracke, B.; Ysebaert, D.; Michielsen, P.; Francque, S.; Vanwolleghem, T.; Verlinden, A.

    2017-01-01

    Background and Aims: Due to the shortage of donor livers, minor ABO-incompatible liver transplantations are commonly performed. Together with the allograft, immunocompetent B-lymphocytes, called passenger lymphocytes, are transplanted. In case of minor ABO-incompatibility, these passenger

  19. Human Leukocyte Antigen-DR Expression is Significantly Related to an Increased Disease-Free and Disease-Specific Survival in Patients With Cervical Adenocarcinoma

    NARCIS (Netherlands)

    Samuels, Sanne; Spaans, Vivian M.; Osse, Michelle; Peters, Lex A. W.; Kenter, Gemma G.; Fleuren, Gertjan J.; Jordanova, Ekaterina S.

    2016-01-01

    Human leukocyte antigen (HLA) class II antigens are expressed on antigen-presenting cells, that is, macrophages, dendritic cells, and B lymphocytes. Under the influence of IFN-γ, HLA class II molecules can also be expressed on T lymphocytes, epithelial and endothelial cells. In addition, HLA class

  20. Specific blockade by CD54 and MHC II of CD40-mediated signaling for B cell proliferation and survival

    DEFF Research Database (Denmark)

    Doyle, I S; Hollmann, C A; Crispe, I N

    2001-01-01

    Regulation of B lymphocyte proliferation is critical to maintenance of self-tolerance, and intercellular interactions are likely to signal such regulation. Here, we show that coligation of either the adhesion molecule ICAM-1/CD54 or MHC II with CD40 inhibited cell cycle progression and promoted a...

  1. Splenic marginal zone lymphoma in a HIV-1 infected patient: evidence favouring a pathogenetic role of HIV-1 itself in the lymphomagenesis.

    Science.gov (United States)

    Cagliuso, M; Conti, V; Trasarti, S; Lombardi, L; Riminucci, M; Perez, M; Turriziani, O; Falasca, F; Nanni, M; Tafuri, A; Mezzaroma, I

    2013-02-01

    A rare case of splenic marginal zone lymphoma (SMZL) in a human immunodeficiency virus (HIV)-1 infected patient is described. As an association between SMZL and viral infections has been reported, the presence of the hepatitis C virus and HIV-1 genomes was evaluated. Only HIV-1 DNA levels were detected in enriched splenic B lymphocytes, suggesting a HIV-1 involvement in lymphomagenesis.

  2. Bruton's tyrosine kinase gene mutations in Turkish patients with X-linked agammaglobulinemia from a single center: Novel mutations in βTK gene

    NARCIS (Netherlands)

    Ç. Aydoǧmuş (Çiǧdem); Y. Camcioǧlu (Yildiz); M. van der Burg (Mirjam); H. Çokuǧraş (H.); N. Akçakaya (Necla); J.J.M. van Dongen (Jacques)

    2013-01-01

    textabstractObjective: X-linked agammaglobulinemia (XLA) is caused by a mutation in the Bruton's tyrosine kinase gene and is characterized by a delay in the maturation and differentiation of B lymphocytes. Patients with XLA have either absent or very low levels of circulating mature B cells (<1%),

  3. B and T cell screen

    Science.gov (United States)

    E-rosetting; T and B lymphocyte assays; B and T lymphocyte assays ... identifiers are added to distinguish between T and B cells. ... the following, which might affect your T and B cell count: Chemotherapy HIV/AIDS Radiation therapy Recent ...

  4. Rituximab (MabThera) til behandling af aktiv reumatoid artritis

    DEFF Research Database (Denmark)

    El Fassi, Daniel; Nielsen, Claus Henrik; Bendtzen, Klaus

    2006-01-01

    Rituximab (RTX) is a murine/human monoclonal antibody to CD20, a protein expressed almost exclusively on human B-lymphocytes. RTX induces rapid and marked B-cell depletion with beneficial clinical effects in 1/3 to 1/2 of rheumatoid arthritis patients. Treatment is given as two iv. infusions with...

  5. Role B lymfocytů v patogenezi revmatoidní artritidy. II. detekce CD19+B lymfocytů specifických pro peptidy obsahující citrulin v periferní krvi a synoviální pacientů s revmatoidní artritidou

    Czech Academy of Sciences Publication Activity Database

    Růžičková, Š.; Cimburek, Zdeněk; Moravcová, T.; Hůzlová, Z.; Veselá, I.; Kryštůfková, O.; Vencovský, J.

    2005-01-01

    Roč. 19, č. 3 (2005), s. 81-86 ISSN 1210-1931 R&D Projects: GA MZd NK7273 Institutional research plan: CEZ:AV0Z50200510 Keywords : rheumatoid arthritis * B lymphocytes * autoantigen Subject RIV: EE - Microbiology, Virology

  6. All projects related to | Page 23 | IDRC - International Development ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    The two faces of endogenous DNA editing enzymes: Promoting gene mutations as well as genome repair. Project. Type B lymphocytes are a specific type of white blood cell within our immune system. Region: India, Pakistan, Canada, Israel. Program: Foundations for Innovation. Total Funding: CA$ 498,669.00.

  7. All projects related to | Page 22 | IDRC - International Development ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    The two faces of endogenous DNA editing enzymes: Promoting gene mutations as well as genome repair. Project. Type B lymphocytes are a specific type of white blood cell within our immune system. Region: India, Pakistan, Canada, Israel. Program: Foundations for Innovation. Total Funding: CA$ 498,669.00.

  8. Search Results | Page 15 | IDRC - International Development ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Results 141 - 150 of 1804 ... The two faces of endogenous DNA editing enzymes: Promoting gene mutations as well as genome repair. Type B lymphocytes are a specific type of white blood cell within our immune system. They produce and export antibodies which seek out, attach to, and neutralize microbes and toxins.

  9. Immunohistochemical evaluation of lymphocyte populations in the ...

    African Journals Online (AJOL)

    Here we sought to quantify T and B lymphocyte populations in the lacrimal tissue of the nictitans glands of dogs with iKCS those with neurological KCS (nKCS)and also in dogs with tear production within the recognized normal levels and no ocular surface signs of KCS. Nictitans glands were obtained from 10 healthy dogs ...

  10. Production and purification of polyclonal anti-hamster ...

    African Journals Online (AJOL)

    user

    2011-01-17

    Jan 17, 2011 ... Purified antibody and its conjugation with HRP are used in research and diagnosis of hamster disease. Key words: Production, purification, hamster immunoglobulins. INTRODUCTION. Polyclonal antibodies represent a group or mixture of antibodies produced by different B-lymphocytes in res- ponse to the ...

  11. The expression of SLAMF7 levels in malignant B cells: a novel ...

    African Journals Online (AJOL)

    Signalling lymphocyte activation molecule (SLAM) F7 is found on the surface of some immune cells including B-lymphocytes. Its activation leads to the proliferation or differentiation of immune cells. The objectives of the study were to measure SLAMF7 expression levels on B-CLL cells, and to upregulate the expression of ...

  12. Separation and properties of EA-rosette-forming lymphocytes in humans

    NARCIS (Netherlands)

    van Oers, M. H.; Zeijlemaker, W. P.; Schellekens, P. T.

    1977-01-01

    Human peripheral blood lymphocytes were separated into subpopulations enriched or depleted with respect to B lymphocytes (Ig-bearing cells), T lymphocytes, (cell forming rosettes with sheep erythrocytes: E-RFC) and Fc receptor-bearing lymphocytes (EA-RFC). From the distributions and recoveries of

  13. Gene expression analysis uncovers similarity and differences among Burkitt lymphoma subtypes

    DEFF Research Database (Denmark)

    Piccaluga, Pier Paolo; De Falco, Giulia; Kustagi, Manjunath

    2011-01-01

    Burkitt lymphoma (BL) is classified into 3 clinical subsets: endemic, sporadic, and immunodeficiency-associated BL. So far, possible differences in their gene expression profiles (GEPs) have not been investigated. We studied GEPs of BL subtypes, other B-cell lymphomas, and B lymphocytes; first, w...

  14. JUNE NJCP 2009 FINAL sp.cdr

    African Journals Online (AJOL)

    User

    All the parents of the patients had access to cars and 75% resided ... cells. It is covered by a pseudostratified ciliated columnar epithelium rich in goblet cells, plicated to form numerous surface folds which increase the total surface area. It is rich in lymphocytes, mainly B- lymphocytes and small T-lymphocytes and very few.

  15. Failure of lymphocyte-membrane HLA-A and -B expression in two siblings with combined immunodeficiency

    NARCIS (Netherlands)

    Schuurman, R.K.B.; Rood, J.J. van; Vossen, J.M.; Schellekens, P.Th.A.; Feltkamp-Vroom, Th.M.; Doyer, E.; Gmelig Meyling, F.H.J.; Visser, H.K.A.

    1979-01-01

    A diagnosis of partial combined immunodeficiency was made in two Turkish siblings with a history of multiple pyogenic infections and persistent candidiasis. They demonstrated severe hypo-γ-globulinemia, with B-lymphocytes, but deficient plasma cell differentiation. T-Lymphocytes were decreased in

  16. Mutations in CHD7 in patients with CHARGE syndrome cause T-B + natural killer cell + severe combined immune deficiency and may cause Omenn-like syndrome.

    NARCIS (Netherlands)

    Gennery, A.R.; Slatter, M.A.; Rice, J.; Hoefsloot, L.H.; Barge, D.; McLean-Tooke, A.; Montgomery, T.; Goodship, J.A.; Burt, A.D.; Flood, T.J.; Abinun, M.; Cant, A.J.; Johnson, D.

    2008-01-01

    More than 11 genetic causes of severe combined immunodeficiency (SCID) have been identified, affecting development and/or function of T lymphocytes, and sometimes B lymphocytes and natural killer (NK) cells. Deletion of 22q11.2 is associated with immunodeficiency, although less than 1% of cases are

  17. Strong and selective glomerular localization of CD134 ligand and TNF receptor-1 in proliferative lupus nephritis

    NARCIS (Netherlands)

    Aten, J.; Roos, A.; Claessen, N.; Schilder-Tol, E. J.; ten Berge, I. J.; Weening, J. J.

    2000-01-01

    CD134 (OX40) is a member of the tumor necrosis factor (TNF) receptor (TNFR) family that can be expressed on activated T lymphocytes. Interaction between CD134 and its ligand (CD134L) is involved in costimulation of T and B lymphocyte activation, and in T cell adhesion to endothelium. To examine the

  18. Nye behandlinger af Graves' sygdom med fokus på det B-lymfocyt-depleterende antistof rituximab

    DEFF Research Database (Denmark)

    Nielsen, Claus Henrik; El Fassi, Daniel; Hegedüs, Laszlo

    2008-01-01

    Graves' disease (GD) is caused by autoantibodies to the thyrotropin receptor (TRAb). In a controlled study using the B-lymphocyte depleting agent rituximab (RTX), an RTX-specific effect was found on long-term remission following methimazole (MMI) therapy. However, benefits were limited to patient...... in uncomplicated GD. The potential use of other immunomodulatory agents in GD is discussed....

  19. How do we avoid developing allergy: Modifications of the T(H)2 response from a B-cell perspective

    NARCIS (Netherlands)

    Aalberse, Rob C.; Platts-Mills, Thomas A. E.

    2004-01-01

    The synthesis of IgE by B cells occurs at a low rate compared with that of other antibodies, even in allergic subjects. One rate-limiting step is the class switch, by which B lymphocytes switch to produce immunoglobulin epsilon heavy chains rather than mu or gamma heavy chains. We propose an

  20. A high-affinity human monoclonal IgM antibody reacting with multiple strains of Mycoplasma hominis

    DEFF Research Database (Denmark)

    Moller, SA; Birkelund, Svend; Borrebaeck, CA

    1990-01-01

    Human monoclonal antibodies were produced against Mycoplasma hominis by in vitro immunization of peripheral blood lymphocytes from a healthy seropositive donor using low amounts of antigen (5 ng/ml). The immune B lymphocytes were subsequently immortalized by Epstein-Barr virus transformation foll...

  1. Experiment list: SRX080394 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available erm|Description=B-lymphocyte, lymphoblastoid, International HapMap Project, CEPH/Utah, treatment: Epstein-Ba...f=GM06990 || cell=GM06990 || cell organism=Human || cell description=Lymphoblastoid, International HapMap Project

  2. Experiment list: SRX100914 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ription=B-lymphocyte, lymphoblastoid, International HapMap Project - CEPH/Utah - European Caucasion, Epstein...lastoid, International HapMap Project - CEPH/Utah - European Caucasion, Epstein-Barr Virus || controlid=GM12...lastoid, International HapMap Project - CEPH/Utah - European Caucasion, Epstein-Barr Virus || cell karyotype

  3. Properties of mouse CD40: differential expression of CD40 epitopes on dendritic cells and epithelial cells

    NARCIS (Netherlands)

    van den Berg, T. K.; Hasbold, J.; Renardel de Lavalette, C.; Döpp, E. A.; Dijkstra, C. D.; Klaus, G. G.

    1996-01-01

    In this study we describe the tissue distribution of mouse CD40 using two monoclonal antibodies (mAb) against different epitopes of the molecule. In lymphoid tissues CD40 was expressed by B lymphocytes. Most B cells in typical B-cell compartments were CD40-positive, including germinal centre B

  4. Functional Epstein-Barr virus reservoir in plasma cells derived from infected peripheral blood memory B cells.

    Science.gov (United States)

    Al Tabaa, Yassine; Tuaillon, Edouard; Bollore, Karine; Foulongne, Vincent; Petitjean, Gael; Seigneurin, Jean-Marie; Duperray, Christophe; Desgranges, Claude; Vendrell, Jean-Pierre

    2009-01-15

    The Epstein-Barr virus (EBV) causes infectious mononucleosis, establishes latency in resting memory B lymphocytes, and is involved in oncogenesis through poorly understood mechanisms. The EBV lytic cycle is initiated during plasma cell differentiation by mRNAs transcripts encoded by BZLF1, which induce the synthesis of EBV proteins such as the immediate-early antigen ZEBRA and the late membrane antigen gp350. Therefore, we assessed the capacity of circulating EBV-infected B lymphocytes from healthy EBV-seropositive subjects to enter and complete the EBV lytic cycle. Purified B lymphocytes were polyclonally stimulated and BZLF1- or gp350-secreting cells (BZLF1-SCs or gp350-SCs) were enumerated by ELISpot assays. The number of BZLF1-SCs ranged from 50 to 480/107 lymphocytes (median, 80; 25th-75th percentiles, 70-150) and gp350-SCs from 10 to 40/107 lymphocytes (median, 17; 25th-75th percentiles, 10-20). gp350-SCs represented only 7.7% to 28.6% of BZLF1-SCs (median, 15%; 25th-75th percentiles, 10.5%-20%). This EBV functional reservoir was preferentially restricted to plasma cells derived from CD27(+) IgD(-) memory B lymphocytes. In 9 of 13 subjects, EBV DNA quantification in B-cell culture supernatants gave evidence of completion of EBV lytic cycle. These results demonstrate that EBV proteins can be secreted by EBV-infected B lymphocytes from healthy carriers, a majority generating an abortive EBV lytic cycle and a minority completing the cycle.

  5. Inhibition of autoimmune diabetes in nonobese diabetic mice by transgenic restoration of H2-E MHC class II expression: additive, but unequal, involvement of multiple APC subtypes.

    Science.gov (United States)

    Johnson, E A; Silveira, P; Chapman, H D; Leiter, E H; Serreze, D V

    2001-08-15

    Transgenic restoration of normally absent H2-E MHC class II molecules on APC dominantly inhibits T cell-mediated autoimmune diabetes (IDDM) in nonobese diabetic (NOD) mice. We analyzed the minimal requirements for transgenic H2-E expression on APC subtypes (B lymphocytes vs macrophages/dendritic cells (DC)) to inhibit IDDM. This issue was addressed through the use of NOD stocks transgenically expressing high levels of H2-E and/or made genetically deficient in B lymphocytes in a series of genetic intercross and bone marrow/lymphocyte chimera experiments. Standard (H2-E(null)) NOD B lymphocytes exert a pathogenic function(s) necessary for IDDM. However, IDDM was inhibited in mixed chimeras where H2-E was solely expressed on all B lymphocytes. Interestingly, this resistance was abrogated when even a minority of standard NOD H2-E(null) B lymphocytes were also present. In contrast, in NOD chimeras where H2-E expression was solely limited to approximately half the macrophages/DC, an active immunoregulatory process was induced that inhibited IDDM. Introduction of a disrupted IL-4 gene into the NOD-H2-E transgenic stock demonstrated that induction of this Th2 cytokine does not represent the IDDM protective immunoregulatory process mediated by H2-E expression. In conclusion, high numbers of multiple subtypes of APC must express H2-E MHC class II molecules to additively inhibit IDDM in NOD mice. This raises a high threshold for success in future intervention protocols designed to inhibit IDDM by introduction of putatively protective MHC molecules into hemopoietic precursors of APC.

  6. State of immune system of patients with infectious-allergic asthma subjected to transcerebral exposure to UHF electron field (27, 12 MHz)

    Energy Technology Data Exchange (ETDEWEB)

    Bogolyubov, V.M.; Malyavin, A.G.; Pershin, S.B.; Shubina, A.V.; Kubli, S.Kh.; Myshelova, K.P.

    An attempt was made to affect immunologic reactions in infectious-allergic asthma patients by subjecting them to transcerebral exposure to UHF electric field. Seventy-six patients, aged 23 to 69 years with varying duration of the disease, were studied. The treatment consisted of 25 exposures lasting from 5 to 15 min; a sham exposure was used on ten patients serving as controls. In all, 55/66 patients experienced clinical improvement lasting 6 to 12 months; only 2/10 control patients had any improvement. After the exposure, the level of T-lymphocytes increased along with blood histamine level; no significant changes were observed in case of B-lymphocytes. This immunologic correction was most effective in patients with atopy, with decreased levels of T-lymphocytes and elevated levels of B-lymphocytes. 12 references.

  7. B cell follicle-like structures in multiple sclerosis-with focus on the role of B cell activating factor

    DEFF Research Database (Denmark)

    Morten, Haugen; Frederiksen, Jette L; Vinter, Matilda Degn

    2014-01-01

    B lymphocytes play an important role in the pathogenesis of multiple sclerosis (MS). Follicle-like structures (FLS) have recently been found in the subarachnoid space in the leptomeninges in some patients with secondary progressive MS (SPMS). They contain proliferating B lymphocytes, plasma cells......, helper T lymphocytes and a network of follicular dendritic cells. FLS have been shown to correlate with increased cortical demyelination, neuronal loss, meningeal infiltration and central nervous system inflammation, as well as lower age at disease onset and progression to severe disability and death....... In this review, we will discuss the role of FLS in MS pathogenesis and disease course and the possible influence by B cell activating factor (BAFF) and C-X-C motif chemokine 13 (CXCL13)....

  8. B and T lymphocytes in man. I. Effect of infant thymic irradiation on the circulating B and T lymphocytes

    International Nuclear Information System (INIS)

    Reddy, M.M.; Goh, K.; Hempelmann, L.H.

    1976-01-01

    B and T lymphocytes were studied in a group of adults whose thymic glands were irradiated in infancy for alleged thymic enlargement. Two independent methods were used to determine the B and T lymphocytes from each peripheral blood specimen: (1) the relative proportion of cells with surface immunoglobulins (B lymphocytes) and cells forming rosettes with sheep erythrocytes (T lymphocytes); and (2) the relative mitogenic response to phytohemagglutinin (T lymphocytes) and to pokeweed mitogen (B lymphocytes). All specimens were coded. The results obtained indicate: (1) a reduction of B and T lymphocytes; and (2) a decreased mitogenic response of lymphocytes to phytohemagglutinin and pokeweed mitogen in this group of patients as compared with the controls. These observations suggest that (1) the effect of irradiation to the thymus gland on lymphocytes is long lasting and (2) both B and T lymphocytes are affected by irradiation to the thymus gland

  9. Effect of levamisole and methisoprinol on in vitro lymphocyte reactivity in chronically irradiated subjects and patients affected by neoplasias

    Energy Technology Data Exchange (ETDEWEB)

    Campo, M.; Chiavaro, I.; Canfarotta, C.; Stivala, F.; Berrardini, A.

    1982-01-01

    The data of this experiment show that Levamisole moderately stimulates T-lymphocyte proliferation and efficiency in vitro and methisoprinol markedly does so when both drugs act in combination with PHA in subjects with severely impaired cell-mediated responsiveness, whereas they do not exert any effect on lymphocytes in normal subjects. B-lymphocyte in vitro responsiveness does not appear to be affected by the immunomodulators, except for some cases of cancer of the stomach wherein B-lymphocyte responsiveness is stimulated in vitro by Levamisole and more evidently by Methisoprinol. These data support the use of Methisoprinol or Levamisole in therapy, and further investigations regarding the mechanisms whereby they might act and the dose-effect relationship which might show to be important for the type of desired immunomodulation would appear appropriate.

  10. Expression of nicotinic acetylcholine receptors on human B-lymphoma cells

    Directory of Open Access Journals (Sweden)

    Skok M. V.

    2009-12-01

    Full Text Available Aim. To find a correlation between the level of nicotinic acetylcholine receptor (nAChR expression and B lymphocyte differentiation or activation state. Methods. Expression of nAChRs in the REH, Ramos and Daudi cell lines was studied by flow cytometry using nAChR subunit-specific antibodies; cell proliferation was studied by MTT test. Results. It is shown that the level of 42/4 and 7 nAChRs expression increased along with B lymphocyte differentiation (Ramos > REH and activation (Daudi > > Ramos and depended on the antigen-specific receptor expression. The nAChR stimulation/blockade did not influence the intensity of cell proliferation.

  11. Disturbances of cell-mediated immunity in ornithosis.

    Science.gov (United States)

    Konopka, L; Koba, S; Partyka, M; Maślanka, K; Kryczka, W; Szerszén, B; Bartosz, B

    1984-01-01

    27 cases of ornithosis were observed during an epidemia in 1980 in Kielce and subsequently followed with respect to immunological characteristics of peripheral blood lymphocytes. Blastic transformation of these cells was tested after stimulation in vitro with three different mitogens. Identification of peripheral blood T and B lymphocytes was done using rosette tests (E,EA,EAC) and the occurrence of surface immunoglobulins was determined by the immunofluorescent method with polyvalent anti-immunoglobulin serum. The counts of T and B lymphocytes in the peripheral blood were normal throughout the whole period of the observation, but from the 3rd week on a significant impairment of 3H-thymidine incorporation into the cells stimulated with Con A was observed, and from the 10th week on, this impairment appeared also in cells stimulated with PHA and PWM. These observations revealed considerable disturbances in cell-mediated reactivity in patients with ornithosis and seem to be connected with chronic infection with Chlamydia psittaci.

  12. Application of carrier testing to genetic counseling for X-linked agammaglobulinemia

    Energy Technology Data Exchange (ETDEWEB)

    Allen, R.C.; Nachtman, R.G.; Belmont, J.W.; Rosenblatt, H.M.

    1994-01-01

    Bruton X-linked agammaglobulinemia (XLA) is a phenotypically recessive genetic disorder of B lymphocyte development. Female carriers of XLA, although asymptomatic, have a characteristic B cell lineage-specific skewing of the pattern of X inactivation. Skewing apparently results from defective growth and maturation of B cell precursors bearing a mutant active X chromosome. In this study, carrier status was tested in 58 women from 22 families referred with a history of agammaglobulinemia. Primary carrier analysis to examine patterns of X inactivation in CD19[sup +] peripheral blood cells (B lymphocytes) was conducted using quantitative PCR at the androgen-receptor locus. Obligate carriers of XLA demonstrated >95% skewing of X inactivation in peripheral blood CD19[sup +] cells but not in CD19[sup [minus

  13. Compounds from the Chinese black ant (Polyrhachis dives) and NMR behavior of the isomers with formamide group.

    Science.gov (United States)

    Tang, Jian-Jun; Luo, Qi; Di, Lei; Zhang, Li; Lu, Qing; Hou, Bo; Zuo, Zhi-Li; Xia, Hou-Lin; Ma, Xiu-Jing; Cheng, Yong-Xian

    2015-01-01

    Two new dopamine derivatives divesamides A (1) and B (2), along with six known N-containing compounds were isolated from the Chinese black ant (Polyrhachis dives). Their structures were determined on the basis of spectroscopic methods. Compound 1 is a racemate, and chiral HPLC separation yielded a pair of antipodes. The absolute configuration of (+)-1 was assigned by a computational method. The double signals in the (1)H and (13)C NMR spectra of 2 that resulted from the presence of a formamide group were discussed. The T- and B-lymphocytes proliferation assay showed that 2 has moderate immunosuppressive activity toward T- and B-lymphocytes proliferation at a concentration of 20 μM.

  14. Analysis of the numbers of B, T and subpopulation lymphocytes in patients with breast cancer submitted to a different radiotherapy schedules

    International Nuclear Information System (INIS)

    Andrade, J.M. de.

    1989-01-01

    The behaviour of T and B lymphocytes subpopulations was evaluated in patients with breast cancer submitted to 3 different schedules of radiotherapy. The assays were carried out before and immediately after the end of treatment. T lymphocytes and the helper/inducer (CD 4 ) and suppressor/cytotoxic (CD 8 ) subpopulations were counted by indirect immunofluorescence with monoclonal antibodies of the OKT series. The number of B lymphocytes was obtained by direct immunofluorescence with fluorescein-conjugated anti-human Ig antibodies. The patients were divided into 3 groups: irradiation of the breast only; irradiation of the lymph-draining areas; irradiation of the breast, of the lymph-draining area and of the sternal area. (author)

  15. Distribution of 51Cr labeled leukemia cells in mice: Comparison with representative normal cells

    International Nuclear Information System (INIS)

    Boranic, M.; Radacic, M.

    1978-01-01

    Cells of two transplantable leukemias of mice, one myeloid and one lymphoid, were labeled with 51 Cr in order to follow their distribution in hemopoietic and parenchymatous organs and blood of syngeneic recipients. Distribution of myeloid leukemia cells was compared with that of regenerating bone marrow cells and normal spleen cells. The organ distribution of myeloid leukemia cells was essentially different from that of cells of regenerating bone marrow, and both were different from that of normal spleen cells. Cells of lymphoid leukemia, which are presumably of B-lymphocyte origin, were compared with a B-lymphocyte enriched population, obtained from the lymph nodes of so-called TIR mice (thymectomized, irradiated, and reconstituted with syngeneic bone marrow), and with spleen cells of normal mice. The three patterns of organ distribution were different. It is concluded that the two leukemias studied each have a specific and characteristic distribution. (author)

  16. SUMOylation of Blimp-1 promotes its proteasomal degradation.

    Science.gov (United States)

    Shimshon, Livnat; Michaeli, Avital; Hadar, Rivka; Nutt, Stephen L; David, Yael; Navon, Ami; Waisman, Ari; Tirosh, Boaz

    2011-08-04

    B lymphocyte induced maturation protein-1 (Blimp-1) is a transcription repressor of the Krueppel-like family. Blimp-1 plays important roles in developmental processes, such as of germ cells and hair follicle stem cells. In B lymphocytes Blimp-1 orchestrates the terminal differentiation into plasma cells. We discovered that Blimp-1 undergoes SUMOylation by SUMO-1. This SUMOylation is modulated by the SUMO protease SENP1. While Blimp-1 is relatively stable in 293T cells, a fusion with SUMO1 rendered it to rapid proteasomal degradation. Increase in SENP1 activity stabilized Blimp-1, while a decrease promoted its degradation. Our data indicate that SUMOylation of Blimp-1 regulates its intracellular stability. Copyright © 2011 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  17. Participação de células B-1b noprocesso de cicatrização no camundongo

    OpenAIRE

    Oliveira, Helena da Cruz [UNIFESP

    2010-01-01

    Wound healing is a complex phenomenon whose mechanisms are not fully understood. There are no reports concerning the participation of B lymphocytes in tissue repair. However, Almeida et al (Inter Immunol, 2001) demonstrated that B-1 cells proliferate in stationary culture of adherent peritoneal cells. Further, that B-1 cells migrate to non-specific inflammatory focus and differentiate into a mononuclear phagocyte. B-1 cells differ from conventional B cell by its anatomical location, ontogeny,...

  18. Suspected primary immune deficiency in a Donge de Bordeaux dog : short communication

    Directory of Open Access Journals (Sweden)

    R.G. Lobetti

    2002-07-01

    Full Text Available A young Donge de Bordeaux dog was presented with chronic intermittent antibiotic responsive gastrointestinal and respiratory disease. Further evaluation showed bacterial lymphadenitis, bacterial tracheitis, normal white cell and differential cell counts, hypogammaglobulinaemia, and the absence of B-lymphocytes but the presence of T-lymphocytes in the lymphoid tissue stained with lymphocyte markers. As the dog came from a narrow genetic base, with related dogs showing similar clinical signs, possible B-cell congenital immune deficiency was suspected.

  19. An extended leukocyte differential count (16 types of circulating leukocytes) using the CytoDiff flow cytometric system can provide information for the discrimination of sepsis severity and prediction of outcome in sepsis patients.

    Science.gov (United States)

    Park, Sang Hyuk; Park, Borae G; Park, Chan-Jeoung; Kim, Sue; Kim, Duck-Hee; Jang, Seongsoo; Hong, Suk-Kyung; Chi, Hyun-Sook

    2014-07-01

    The Beckman Coulter CytoDiff flow cytometric system (Beckman Coulter, Miami, FL) was recently developed for performing leukocyte differential counts in up to 16 leukocyte subpopulations. We compared these leukocyte subpopulation levels among patients with three stages of sepsis (uncomplicated sepsis, severe sepsis, septic shock), especially focused on the discrimination of complicated sepsis from uncomplicated sepsis. We examined a total of 181 samples with sepsis who were admitted to the surgical intensive care unit. In addition, we examined samples obtained from 60 normal healthy volunteers. Both the proportions and absolute numbers of each cell type in the four groups were obtained using the CytoDiff flow cytometric system and compared. Mature neutrophils and immature granulocytes failed to discriminate patients with complicated sepsis from those with uncomplicated sepsis although their absolute numbers were increased compared with normal controls. In contrast, almost all lymphocyte subpopulations and CD16(-) monocytes decreased significantly in patients with complicated sepsis compared with uncomplicated sepsis. Among them, only B lymphocytes showed independent ability to discriminate two groups. Both B lymphocytes and CD16(-) monocytes possessed a significant adverse prognostic impact on overall survival when their absolute numbers decreased. Almost all lymphocyte subpopulations and CD16(-) monocytes decrease in size with increasing sepsis severity. Among them, only B lymphocytes showed independent ability to discriminate patients with complicated sepsis from those with uncomplicated sepsis. Both B lymphocytes and CD16 (-) monocytes show a significant adverse prognostic impact on overall survival outcomes in sepsis patients when their absolute numbers are decreased. Copyright © 2013 Clinical Cytometry Society.

  20. [Lymphocyte subpopulations in alopecia areata].

    Science.gov (United States)

    Calandria, L; Paciel, J; Bruno, J; Martini, M; Vignale, R; Civila, E

    1986-01-01

    Subsets of peripheral blood lymphocytes were studied in 19 patients with alopecia areata. The results shows: a decreased Tm/Tg ratio, decreased number of OKT4+ cells, increased OKT8+ cells, decreased OKT4+/OKT8+ cell ratio. Total lymphocytes, T cells, Tm cells, Tg cells, T DR+ cells and B lymphocytes were normal. The results are similar to those founded in autoimmune diseases and suggest the existence of an immunopathogenic mechanism in these disease.

  1. Impact of the B Cell Growth Factor APRIL on the Qualitative and Immunological Characteristics of Atherosclerotic Plaques.

    Science.gov (United States)

    Bernelot Moens, Sophie J; van Leuven, Sander I; Zheng, Kang H; Havik, Stefan R; Versloot, Miranda V; van Duivenvoorde, Leonie M; Hahne, Michael; Stroes, Erik S G; Baeten, Dominique L; Hamers, Anouk A J

    2016-01-01

    Studies on the role of B lymphocytes in atherosclerosis development, have yielded contradictory results. Whereas B lymphocyte-deficiency aggravates atherosclerosis in mice; depletion of mature B lymphocytes reduces atherosclerosis. These observations led to the notion that distinct B lymphocyte subsets have different roles. B1a lymphocytes exert an atheroprotective effect, which has been attributed to secretion of IgM, which can be deposited in atherosclerotic lesions thereby reducing necrotic core formation. Tumor necrosis factor (TNF)-family member 'A Proliferation-Inducing Ligand' (APRIL, also known as TNFSF13) was previously shown to increase serum IgM levels in a murine model. In this study, we investigated the effect of APRIL overexpression on advanced lesion formation and composition, IgM production and B cell phenotype. We crossed APRIL transgenic (APRIL-Tg) mice with ApoE knockout (ApoE-/-) mice. After a 12-week Western Type Diet, ApoE-/-APRIL-Tg mice and ApoE-/- littermates showed similar increases in body weight and lipid levels. Histologic evaluation showed no differences in lesion size, stage or necrotic area. However, smooth muscle cell (α-actin stain) content was increased in ApoE-/-APRIL-Tg mice, implying more stable lesions. In addition, increases in both plaque IgM deposition and plasma IgM levels were found in ApoE-/-APRIL-Tg mice compared with ApoE-/- mice. Flow cytometry revealed a concomitant increase in peritoneal B1a lymphocytes in ApoE-/-APRIL-Tg mice. This study shows that ApoE-/-APRIL-Tg mice have increased oxLDL-specific serum IgM levels, potentially mediated via an increase in B1a lymphocytes. Although no differences in lesion size were found, transgenic ApoE-/-APRIL-Tg mice do show potential plaque stabilizing features in advanced atherosclerotic lesions.

  2. Immunological and epidemiological investigations in regions contaminated by radionuclides after the Chernobyl accident

    International Nuclear Information System (INIS)

    Shubik, V.M.

    1997-01-01

    We have carried out in Novozybkov district of Bryansk region, Russia, immunologic inspection of residents with simultaneous evaluation of radionuclides content in the body and individual dose burden. We have not found any correlation between the dose and immune characteristics: amount of T and B lymphocytes, antibodies level. Only 3 months after the accident increased level of antibodies against thyroid antigens, thyroglobulin and microsomes was found at thyroid doses over 75 cGy. 3 tabs

  3. Circulating clonotypic B cells in multiple myeloma and monoclonal gammopathy of undetermined significance.

    Science.gov (United States)

    Thiago, Leandro S; Perez-Andres, Martin; Balanzategui, Ana; Sarasquete, Maria E; Paiva, Bruno; Jara-Acevedo, Maria; Barcena, Paloma; Sanchez, Maria Luz; Almeida, Julia; González, Marcos; San Miguel, Jesus F; Garcia-Sanz, Ramón; Orfao, Alberto

    2014-01-01

    The B-cell compartment in which multiple myeloma stem cells reside remains unclear. We investigated the potential presence of mature, surface-membrane immunoglobulin-positive B lymphocytes clonally related to the tumor bone marrow plasma cells among different subsets of peripheral blood B cells from ten patients (7 with multiple myeloma and 3 with monoclonal gammopathies of undetermined significance). The presence of clonotypic immunoglobulin heavy chain gene rearrangements was determined in multiple highly-purified fractions of peripheral blood B-lymphocytes including surface-membrane IgM(+) CD27(-) naïve B-lymphocytes, plus surface-membrane IgG(+), IgA(+) and IgM(+) memory CD27(+) B cells, and normal circulating plasma cells, in addition to (mono)clonal plasma cells, by a highly-specific and sensitive allele-specific oligonucleotide polymerase chain reaction directed to the CDR3 sequence of the rearranged IGH gene of tumor plasma cells from individual patients. Our results showed systematic absence of clonotypic rearrangements in all the different B-cell subsets analyzed, including M-component isotype-matched memory B-lymphocytes, at frequencies <0.03 cells/μL (range: 0.0003-0.08 cells/μL); the only exception were the myeloma plasma cells detected and purified from the peripheral blood of four of the seven myeloma patients. These results indicate that circulating B cells from patients with multiple myeloma and monoclonal gammopathies of undetermined significance are usually devoid of clonotypic B cells while the presence of immunophenotypically aberrant myeloma plasma cells in peripheral blood of myeloma patients is a relatively frequent finding.

  4. The Ebf1 knockout mouse and glomerular maturation

    OpenAIRE

    Schmidt-Ott, K.M.

    2014-01-01

    Mice deficient in the transcription factor early B-cell factor 1 (Ebf1) lack mature B lymphocytes but have additional phenotypes suggesting functions outside the hematopoietic system. Fretz et al. report that these mice also exhibit quantitative and qualitative developmental renal defects and develop progressive podocyte foot process effacement. The findings not only suggest that Ebf1 may be pivotal to the transcriptional podocyte network, but also illustrate the importance of distinguishing ...

  5. Optimization of Immunoglobulin Substitution Therapy by a Stochastic Immune Response Model

    OpenAIRE

    Figge, Marc Thilo

    2009-01-01

    BACKGROUND: The immune system is a complex adaptive system of cells and molecules that are interwoven in a highly organized communication network. Primary immune deficiencies are disorders in which essential parts of the immune system are absent or do not function according to plan. X-linked agammaglobulinemia is a B-lymphocyte maturation disorder in which the production of immunoglobulin is prohibited by a genetic defect. Patients have to be put on life-long immunoglobulin substitution thera...

  6. B cell attracting chemokine 1 (CXCL13) and its receptor CXCR5 are expressed in normal and aberrant gut associated lymphoid tissue

    OpenAIRE

    Carlsen, H S; Baekkevold, E S; Johansen, F-E; Haraldsen, G; Brandtzaeg, P

    2002-01-01

    Background and aims: In mice, the B lymphocyte chemoattractant (BLC) CXC chemokine ligand 13 (CXCL13) is sufficient to induce a series of events leading to the formation of organised lymphoid tissue. Its receptor, CXCR5, is required for normal development of secondary lymphoid tissue. However, the human counterpart, B cell attracting chemokine 1 (BCA-1) has only been detected in the stomach and appendix and not in other parts of normal or diseased gut. Hence to elucidate the potential role of...

  7. Persistent cryptosporidiosis in horses with severe combined immunodeficiency.

    OpenAIRE

    Bjorneby, J M; Leach, D R; Perryman, L E

    1991-01-01

    Cryptosporidial infections were established in five young foals with severe combined immunodeficiency following oral administration of 10(8) Cryptosporidium parvum oocysts. All foals shed oocysts (average of 8 x 10(6) to 2 x 10(8)/g of feces) until death. Inflammation and C. parvum organisms were observed in the common bile duct, duodenum, jejunum, and ileum. Since foals with severe combined immunodeficiency lack functional T and B lymphocytes and are incapable of antigen-specific immune resp...

  8. Effects of Tenghuanglin on injury to splenic lymphocyte induced by microwave radiation in rats

    Directory of Open Access Journals (Sweden)

    Qiong MA

    2015-01-01

    Full Text Available Objective To observe the effects of Tenghuanglin (THL on injury to peripheral T and B lymphocytes induced by microwave radiation in rats, and explore the protective effects of THL against derangement of immunity in rat injury induced by microwave irradiation and its mechanism. Methods Eighty clean male SD rats were randomly divided into normal group (CON group, radiation group (RAD group, AduoLa Fuzhenglin (ADL treatment group and THL treatment group, with 20 rats in each group. Before radiation, rats in ADL group and THL group were treated with ADL and THL respectively by gavage once per day for 7 days. Then, whole body of the rats was respectively exposed to 30 mW/cm2 microwave for 15 min. Rats in CON group were shamradiated. The changes in splenic CD3+, CD4+, CD8+ T lymphocyte subsets and CD45RA+ B lymphocyte subset were analyzed 7 and 14 days after radiation. Results Seven days after radiation, the splenic coefficient of RAD group was lower than that of CON group and THL group (P0.05. The CD45RA+ B cell proportion of RAD group was lower than those of CON group and ADL group 7 days after radiation (P0.05. Conclusions The splenic T and B lymphocytes subsets decrease significantly at the early stage after microwave radiation in rats. Because of the rapid decrease in CD4+ T cell proportion, decreased CD4/CD8 ratio could lead to immune imbalance. Preventive treatment with THL could increase the T and B lymphocyte proportions and improve the CD4/CD8 ratio in rats after microwave radiation. DOI: 10.11855/j.issn.0577-7402.2014.12.14

  9. Post-transplant Lymphoproliferative Disorder Arising from Renal Allograft Parenchyma: A Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Park, Byung Kwan; Kim, Chan Kyo; Kwon, Ghee Young [Samsung Medical Center, Sungkyunkwan University College of Medicine, Seoul (Korea, Republic of)

    2010-06-15

    Post-transplant lymphoproliferative disorder (PTLD) is a rare but serious complication that occurs in patients undergoing kidney transplantation. PTLD usually manifests as a renal hilar mass comprised of histologically B-lymphocytes. We report our experience of managing a patient with PTLD arising from renal parenchyma. Ultrasonographic and MR imaging features of this unusual PTLD suggested differentiated renal cell carcinoma arising from the renal allograft

  10. Mononuclear cell infiltration and its relation to the expression of major histocompatibility complex antigens and adhesion molecules in pancreas biopsy specimens from newly diagnosed insulin-dependent diabetes mellitus patients.

    OpenAIRE

    Itoh, N; Hanafusa, T; Miyazaki, A; Miyagawa, J; Yamagata, K; Yamamoto, K; Waguri, M; Imagawa, A; Tamura, S; Inada, M

    1993-01-01

    We examined pancreas biopsy specimens from 18 newly diagnosed insulin-dependent diabetes mellitus (IDDM) patients to elucidate the mechanism underlying beta cell destruction. Pancreas islets were seen in all patients and insulitis in eight patients. Infiltrating mononuclear cells consisted of CD4+T, CD8+T, B lymphocytes, and macrophages. Among them, CD8+T lymphocytes were predominant and macrophages followed. The expression of MHC class I antigens was increased in islet and endothelial cells ...

  11. Impacts of cigarette smoking on immune responsiveness: Up and down or upside down?

    OpenAIRE

    Qiu, Feifei; Liang, Chun-Ling; Liu, Huazhen; Zeng, Yu-Qun; Hou, Shaozhen; Huang, Song; Lai, Xiaoping; Dai, Zhenhua

    2016-01-01

    Cigarette smoking is associated with numerous diseases and poses a serious challenge to the current healthcare system worldwide. Smoking impacts both innate and adaptive immunity and plays dual roles in regulating immunity by either exacerbation of pathogenic immune responses or attenuation of defensive immunity. Adaptive immune cells affected by smoking mainly include T helper cells (Th1/Th2/Th17), CD4+CD25+ regulatory T cells, CD8+ T cells, B cells and memory T/B lymphocytes while innate im...

  12. CHARACTERIZATION OF TWO MONOCLONAL ANTIBODIES WHICH RECOGNIZE DIFFERENT SUBPOPULATIONS OF CHICKEN T LYMPHOCYTES

    OpenAIRE

    KONDO, Takashi; HATTORI, Masakazu; KODAMA, Hiroshi; ONUMA, Misao; MIKAMI, Takeshi

    1990-01-01

    Distribution among peripheral T lymphocyte subpopulations and biochemical properties of the chicken lymphocyte surface antigens defined by monoclonal antibodies (mAbs) Lc-4 and Lc-6 were examined. Two-color immunofluorescence analysis revealed that Lc-4 and Lc-6 antigens were expressed on mutually exclusive subpopulations of peripheral T lymphocytes but not on B lymphocytes. Lc-4 mAb precipitated a polypeptide with apparent molecular mass of 35 and 65 kilodalton under reducing and non-reducin...

  13. Cell-mediated and humoral immunity in west syndrome

    OpenAIRE

    Montelli, Terezinha C. B.; Iwasso, Maria Tereza R.; Peraçoli, Maria Terezinha S.; Mota, Norma Gerusa S.

    1981-01-01

    The immunological status of five children with West syndrome consequent to previous cerebral lesions was investigated. Three children had West syndrome and two were in transition from West to Lennox-Gastaut syndrome. All of them showed cellular immunological deficiencies in the following tests: sensitization to DNCB, intracutaneous reaction to PHA, inhibition of leucocyte migration, blastic transformation of lymphocytes, T and B lymphocytes in peripheric blood and levels of serum immunoglobul...

  14. An extended leukocyte differential count (16 types of circulating leukocytes) using the cytodiff flow cytometric system can provide informations for the discrimination of sepsis severity and prediction of outcome in sepsis patients.

    Science.gov (United States)

    Park, Sang Hyuk; Park, Borae G; Park, Chan-Jeoung; Kim, Sue; Kim, Duck-Hee; Jang, Seongsoo; Hong, Suk-Kyung; Chi, Hyun-Sook

    2013-08-20

    Background: The Beckman Coulter CytoDiff flow cytometric system (Beckman Coulter, Miami, FL, USA) was recently developed for performing leukocyte differential counts in up to 16 leukocyte subpopulations. We compared these leukocyte subpopulation levels among patients with three stages of sepsis (uncomplicated sepsis, severe sepsis, septic shock), especially focused on the discrimination of complicated sepsis from uncomplicated sepsis. Methods: We examined a total of 181 samples with sepsis who were admitted to the surgical intensive care unit. In addition, we examined samples obtained from 60 normal healthy volunteers. Both the proportions and absolute numbers of each cell type in the four groups were obtained using the CytoDiff flow cytometric system and compared. Results: Mature neutrophils and immature granulocytes failed to discriminate patients with complicated sepsis from those with uncomplicated sepsis although their absolute numbers were increased compared with normal controls. In contrast, almost all lymphocyte subpopulations and CD16(-) monocytes decreased significantly in patients with complicated sepsis compared with uncomplicated sepsis. Among them, only B lymphocytes showed independent ability to discriminate two groups. Both B lymphocytes and CD16(-) monocytes possessed a significant adverse prognostic impact on overall survival when their absolute numbers decreased. Conclusions: Almost all lymphocyte subpopulations and CD16(-) monocytes decrease in size with increasing sepsis severity. Among them, only B lymphocytes showed independent ability to discriminate patients with complicated sepsis from those with uncomplicated sepsis. Both B lymphocytes and CD16(-) monocytes show a significant adverse prognostic impact on overall survival outcomes in sepsis patients when their absolute numbers are decreased. © 2013 Clinical Cytometry Society. Copyright © 2013 Clinical Cytometry Society.

  15. Infringement of cytokines regulation and morphological changes of thyroid gland in Wistar rats with experimental thyrotoxicosis

    OpenAIRE

    V V Zdor; E V Markelova; O M Oleksenko

    2012-01-01

    In view of abundance of autoimmune diseases of thyroid gland, Graves’ Disease in particular, the role of immune regulation and the possibility of controlling it by estimating the function of regulatory T-limphocytes are important questions today. Available for practical estimation of T- and B-lymphocytes tolerance disorder in GBD are serum levels of Th1- and Th2- marker cytokines. Experimental thyrotoxicosis in Wistar rats showed significant increase in serum Il-1α, IFN-γ and Il-10 depending ...

  16. Triggers of IgE class switching and allergy development

    DEFF Research Database (Denmark)

    Poulsen, Lars K.; Hummelshoj, Lone

    2007-01-01

    type 2 (Th2) T cell subset are the actions of thymic stromal lymphopoietin (TSLP) on dendritic cells and the OX40 ligand on CD4+ T cells. In order for a B lymphocyte to switch to IgE production it needs two signals provided by a Th2 cell in the form of the cytokines interleukin (IL-) 4/IL-13...... the need for more knowledge on preventable causes of IgE- and allergy development....

  17. Mechanisms of immune regulation by norepinephrine and cholera toxin

    Energy Technology Data Exchange (ETDEWEB)

    Campbell, K.S.

    1988-01-01

    Norepinephrine has previously been demonstrated by this laboratory to potentiate the in vitro T-dependent antibody response through the stimulation of {beta}-adrenergic receptors. The role of {beta}-adrenergic receptor subtypes in norepinephrine-induced potentiation of the antibody responses was examined with selective {beta}-adrenergic antagonists. The antagonists were metoprolol ({beta}{sub 1}-selective), ICI 118-551 ({beta}{sub 2}-selective), and propranolol ({beta}-non-selective). Both propranolol and ICI 118-551 blocked norepinephrine-induced potentiation of the antibody response, but metoprolol was ineffective. Receptor binding competition of antagonists with the radioligant, ({sup 3}H)CGP-12177 was examined and results were analyzed with the computer program, LIGAND. Competition by ICI 118-551 identified 75% {beta}{sub 2}- and 25% {beta}{sub 1}-adrenergic receptors on splenic mononuclear cells. Enriched T lymphocytes exhibited 75% {beta}{sub 2}-adrenergic receptors, while enriched B lymphocytes contained 90% {beta}{sub 2}-adrenergic receptors as identified by ICI 118-551. Greater than twice as many total receptors were identified on B lymphocytes than T lymphocytes. A T cell lymphoma contained about 60% {beta}{sub 2}-receptors, while 100% were {beta}{sub 2} receptors on a B cell lymphoma, as assessed by ICI 118-551. Results support a heterogeneous {beta}-adrenergic receptor population on T lymphocytes and a more homogeneous {beta}{sub 2}-population on B lymphocytes.

  18. Effects of Al on the splenic immune function and NE in rats.

    Science.gov (United States)

    Hu, Chongwei; Li, Jing; Zhu, Yanzhu; Bai, Chongsheng; Zhang, Jihong; Xia, Shiliang; Li, Yanfei

    2013-12-01

    Norepinephrine (NE) regulates the splenic immune function and it may be related to the effects of Aluminum (Al) on the splenic immune function. Here, the aim of this study was to further explore the effects of aluminum trichloride (AlCl3) on the splenic immune function and its relationship with NE. Forty male Wistar rats were orally exposed to AlCl3 (0, 64.18, 128.36 and 256.72 mg/kg BW) through drinking water for 120 days. The CD3(+), CD4(+), CD8(+) T lymphocytes, the T and B lymphocytes proliferation rates and serum NE concentration were examined. The correlation analysis between splenic immune function and NE were done. The results showed that the CD3(+), CD4(+), CD8(+) T lymphocytes and the T and B lymphocytes proliferation rates decreased and NE concentration increased in AlCl3-treated rats. NE was negatively correlated with proportions of CD3(+), CD4(+) T lymphocytes and T and B lymphocytes proliferation rates, but not correlated with CD8(+) T lymphocytes. The results suggest that AlCl3 suppresses the splenic immune function and NE plays important role in this process. Copyright © 2013 Elsevier Ltd. All rights reserved.

  19. Relations between the stimulation of mixed lymphocyte populations and the staging system according Rai in patients with chronic lymphatic leukemia

    International Nuclear Information System (INIS)

    Heilmann, E.; Venne, U.

    1979-01-01

    By means of the incorporation rate of 3 H thymidine into the lymphocytes of patients with chronic lymphatic leukemia the possibility of stimulating them by using different mitogens was checked and compared with normal persons. The examination covered 11 patients treated with extracorporeal irradiation of the blood (ECIB), 5 patients treated with a chlorambucil therapy, and 10 untreated patients who where classified according to the staging system proposed by Rai. The lymphocytes of the peripheral blood were stimulated as mixed and isolated T and B-lymphocytes in the microculture by using the mitogens PHA, PWM, ConA, and LPS. In all CLL patients there was a diminished stimulation rate of a mixed lymphocyte population. A relation existed between the seriousness of the stage and the deminution of the incorporation rate of 3 H thymidine. A corresponding correlation could not be identified in untreated CLL patients. Isolated T-lymphocytes revealed better results of stimulation than the total population. As to their function B-lymphocytes showed a dependence on the kind of therapy. In the mixed lymphocyte culture of normal persons the best findings could be observed after stimulation with PHA, that is also valid for CLL patients. PHA, PWA, ConA, and LPS were suitable as substances stimulating B-lymphocytes with different efficacy in normal persons and CLL patients. Both collectives showed the best results in the T-lymphocyte culture after stimulation with LPS. (author)

  20. HUMORAL IMMUNOLOGICAL PARAMETERS IN SMOKING AND NON-SMOKING PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE

    Directory of Open Access Journals (Sweden)

    A. G. Kadushkin

    2014-01-01

    Full Text Available Quantitative changes in immunoglobulins A (IgA, IgE, IgG, IgM, and B lymphocytes in peripheral blood were estimated in non-smoking and smoking patients with chronic obstructive pulmonary disease (COPD. The study included 21 non-smoking patients with COPD, 20 smoking patients with COPD, 20 healthy non-smokers, and 21 healthy smokers. The plasma immunoglobulin concentrations were measured by enzyme immunoassay. A B-lymphocyte population was analyzed by flow cytometry. In the smokers with COPD, IgA and IgE levels were significantly higher than those in the smokers without COPD, as well as in the non-smoking patients with COPD versus the healthy non-smokers. An increase in plasma IgG levels occurred only in the smoking patients with COPD. There were no differences in IgM and B lymphocyte levels in both smoking and non-smoking patients with COPD versus the respective groups of healthy individuals. The smoking patients with COPD showed a moderate positive correlation between total plasma IgE levels and smoking index. The findings suggest that IgA, IgE, and IgG are of pathogenetic value.

  1. Alpha-interferon induces enhanced expression of HLA-ABC antigens and beta-2-microglobulin in vivo and in vitro in various subsets of human lymphoid cells

    DEFF Research Database (Denmark)

    Nissen, Mogens Holst; Larsen, J K; Plesner, T

    1987-01-01

    increase of beta-2-m on all subsets investigated. The increase was more pronounced on B lymphocytes (64%) and monocytes (69%) than on T lymphocytes (39%) (P less than 0.01). Also the pretreatment level of beta-2-m was found to be higher on B lymphocytes (0.64 arbitrary units (a.u.)) and monocytes (0.65 a...... with saturating amounts of FITC conjugated monoclonal anti-HLA-ABC or anti-beta-2-m. Phycoerythrin conjugated monoclonal antibodies were simultaneously used for the selection of T lymphocytes. T helper lymphocytes, T suppressor lymphocytes, B lymphocytes and monocytes. In vitro, alpha-IFN induced a significant.......u.) than on T lymphocytes (0.24 a.u.) (P less than 0.001). In vivo, the expression of both HLA-ABC antigens and beta-2-m was studied in three patients 24 h after administration of 50 x 10(6) units alpha-IFN/m2 i.m. HLA-ABC antigens were significantly (P less than 0.05) increased on all subsets investigated...

  2. Rituximab Administration in Third Trimester of Pregnancy Suppresses Neonatal B-Cell Development

    Directory of Open Access Journals (Sweden)

    D. T. Klink

    2008-01-01

    Full Text Available We describe the effect on the neonate of administration of rituximab to a woman with idiopathic thrombocytopenic purpura (ITP. Rituximab, an anti-CD20 antibody, was given weekly for 4 weeks to a woman with ITP in her third trimester of pregnancy. One month after the last rituximab administration a healthy girl was born. She had normal growth and development during the first six months. At birth, B-lymphocytes were not detectable. Rituximab levels in mother and neonate were 24000 and 6700 ng/mL, respectively. Only 7 cases of rituximab administration during pregnancy were described. No adverse events are described for fetus and neonate. We demonstrate that rituximab passes the placenta and inhibits neonatal B-lymphocyte development. However, after 6 months B-lymphocyte levels normalized and vaccination titres after 10 months were adequate. No infection-related complications occurred. Rituximab administration during pregnancy appears to be safe for the child but further studies are warranted.

  3. Antitumor and immune regulation activities of the extracts of some Chinese marine invertebrates

    Science.gov (United States)

    Zhang, Lixin; Fan, Xiao; Han, Lijun

    2005-03-01

    Extracts of 21 marine invertebrates belonging to Coelenterata, Mollusca, Annelida, Bryozoa, Echiura, Arthropoda, Echinodermata and Urochordata were screened for the studies on their antitumor and immune regulation activities. Antitumor activity was determined by MTT method and immune regulation activity was studied using T- and B-lymphocytes in mice spleen in vitro. It was found that the n-butanol part of Asterina pectinifera, the acetic ether part of Tubuaria marina, 95% ethanol extract of Acanthochiton rubrolineatus have a high inhibition rate of 96.7%, 63.9% and 50.5% respectively on tumor cell line HL-60 at the concentration of 0.063 mg/ml. The inhibition rate of the acetic ether part of Tubuaria marina on the tumor cell line A-549 is 65.4% at concentration of 0.063 mg/mL. The 95% ethanol extract of Meretrix meretrix has so outstanding promoting effect on T-lymphocytes that their multiplication increases 25% when the sample concentration is only 1 μg/ml. On B-lymphocytes, the 95% extract of Rapana venosa, at concentration of 100 μg/ml, has a promotion percentage of 60%. On the other hand, under the condition of no cytotoxic effect, the 95% ethanol extracts of Acanthochiton rubrolineatus and Cellana toreum can reach 92% inhibition rate on T lymphocyte at concentration of 100 μg/ml, while the inhibition rate on B lymphocyte of the 95% extract of Acanthochiton rubrolineatus reaches 92% at the same concentration.

  4. A NUP98-HOXD13 leukemic fusion gene leads to impaired class switch recombination and antibody production.

    Science.gov (United States)

    Puthiyaveetil, Abdul Gafoor; Heid, Bettina; Reilly, Christopher M; HogenEsch, Harm; Caudell, David L

    2012-08-01

    Myelodysplastic syndrome is a clonal process characterized by ineffective hematopoiesis and progression to acute leukemia. Although many myelodysplastic syndrome and leukemic patients have compromised immunity, the role of underlying mutations in regulating immune function is poorly understood. Recent studies show that NUP98-HOXD13 (NHD13) fusion gene results in myelodysplastic syndrome and impairs lymphocyte differentiation in transgenic mice. In our studies, we sought to elucidate the mechanism by which NHD13 affects B-lymphocyte development and function. Based on our preliminary findings that transgenic mice had increased levels of IgM and reduced IgG1 and IgE, we hypothesized that the fusion gene might impair class switch recombination (CSR). Mice were immunologically challenged with dinitrophenol. NHD13 mice showed a marked reduction in B-lymphocyte differentiation in their bone marrow and spleen following dinitrophenol stimulation and had reduced production of dinitrophenol-specific antibodies. Spleen follicles from these mice were small and hypocellular, indicating failure of clonal expansion. When isolated NHD13 B lymphocytes were stimulated in vitro using Escherichia coli lipopolysaccharide or lipopolysaccharide + interleukin-4, they failed to undergo sufficient CSR and proliferation. Taken together, our findings show that expression of NUP98-HOXD13 impairs CSR and reduces the antibody-mediated immune response, in addition to its role in leukemia. Further delineation of the NUP98-HOXD13 transgene may reveal novel pathways involved in CSR. Copyright © 2012 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc. All rights reserved.

  5. Expression and in vitro upregulation of MHCII in koala lymphocytes.

    Science.gov (United States)

    Lau, Quintin; Canfield, Paul J; Higgins, Damien P

    2012-06-15

    Understanding and measuring immune activity of the koala (Phascolarctos cinereus), is important to studies of the epidemiology and impact of the widespread chlamydial and koala retroviral (KoRV) infections that occur in this iconic but increasingly threatened species. To explore the interaction of disease and immunity, and to assess the potential for use of class II major histocompatibility complex (MHCII) upregulation as an indicator of lymphocyte activation in in vitro immune assays, we have investigated the expression of MHCII in koala lymphocytes by flow cytometry. MHCII expression was upregulated in mitogen stimulated B lymphocytes in vitro but no such increase was detected in vivo in free-living koalas with active inflammation. In assessing phenotypic baseline data of captive koalas, we have identified that MHCII is expressed predominantly on circulating B lymphocytes (85.7 ± 2.4%) but on very few T lymphocytes (3.4 ± 1.9%), even following activation, and suggest that the latter finding might be compensated by the greater absolute numbers of peripheral blood B lymphocytes in this species relative to many eutherian species. Copyright © 2012 Elsevier B.V. All rights reserved.

  6. Rainbow trout CK9, a CCL25-like ancient chemokine that attracts and regulates B cells and macrophages, the main antigen presenting cells in fish.

    Science.gov (United States)

    Aquilino, Carolina; Granja, Aitor G; Castro, Rosario; Wang, Tiehui; Abos, Beatriz; Parra, David; Secombes, Christopher J; Tafalla, Carolina

    2016-04-05

    CK9 is a rainbow trout (Oncorhynchus mykiss) CC chemokine phylogenetically related to mammalian CCL25. Although CK9 is known to be transcriptionally regulated in response to inflammation particularly in mucosal tissues, its functionality has never been revealed. In the current work, we have demonstrated that CK9 is chemoattractant for antigen presenting cells (APCs) expressing major histocompatibility complex class II (MHC II) on the cell surface. Among these APCs, CK9 has a strong chemotactic capacity for both B cells (IgM+ and IgT+) and macrophages. Along with its chemotactic capacities, CK9 modulated the MHC II turnover of B lymphocytes and up-regulated the phagocytic capacity of both IgM+ cells and macrophages. Although CK9 had no lymphoproliferative effects, it increased the survival of IgT+ lymphocytes. Furthermore, we have established that the chemoattractant capacity of CK9 is strongly increased after pre-incubation of leukocytes with a T-independent antigen, whereas B cell receptor (BCR) cross-linking strongly abrogated their capacity to migrate to CK9, indicating that CK9 preferentially attracts B cells at the steady state or under BCR-independent stimulation. These results point to CK9 being a key regulator of B lymphocyte trafficking in rainbow trout, able to modulate innate functions of teleost B lymphocytes and macrophages.

  7. Missing Links in Antibody Assembly Control

    Directory of Open Access Journals (Sweden)

    Tiziana Anelli

    2013-01-01

    Full Text Available Fidelity of the humoral immune response requires that quiescent B lymphocytes display membrane bound immunoglobulin M (IgM on B lymphocytes surface as part of the B cell receptor, whose function is to recognize an antigen. At the same time B lymphocytes should not secrete IgM until recognition of the antigen has occurred. The heavy chains of the secretory IgM have a C-terminal tail with a cysteine instead of a membrane anchor, which serves to covalently link the IgM subunits by disulfide bonds to form “pentamers” or “hexamers.” By virtue of the same cysteine, unassembled secretory IgM subunits are recognized and retained (via mixed disulfide bonds by members of the protein disulfide isomerase family, in particular ERp44. This so-called “thiol-mediated retention” bars assembly intermediates from prematurely leaving the cell and thereby exerts quality control on the humoral immune response. In this essay we discuss recent findings on how ERp44 governs such assembly control in a pH-dependent manner, shuttling between the cisGolgi and endoplasmic reticulum, and finally on how pERp1/MZB1, possibly as a co-chaperone of GRP94, may help to overrule the thiol-mediated retention in the activated B cell to give way to antibody secretion.

  8. VH repertoire in progeny of long term lymphoid-cultured cells used to reconstitute immunodeficient mice

    International Nuclear Information System (INIS)

    Denis, K.A.; Timson, L.K.; Witte, O.N.

    1989-01-01

    VH gene utilization in the progeny of long term lymphoid-cultured cells used for reconstitution of severe combined immunodeficient mice under varying conditions was determined. Hybridomas made from the spleens of these animals were evaluated for clonality and donor origin and a panel of 146 independent hybridomas were subsequently examined for VH expression. Hybridomas derived from the spleens of SCID mice reconstituted with fresh cells, used as a control, utilized VH families in proportion to their numerical representation in the genome. However, hybridomas from the spleens of mice reconstituted with long term cultured cells utilized a predominance of the two VH gene families most proximal to JH, characteristic of cells early in B lymphocyte development. Coinjection of thymocytes with cultured fetal liver cells, to provide good levels of T lymphocytes, did not alter this pattern of VH utilization. Irradiation (3 Gy) of the mice before cultured cell injection, which leads to more complete reconstitution of the B cell compartment, was effective in removing this bias in the VH repertoire. Hybridomas derived from these mice expressed their VH genes more in proportion to family size, characteristic of cells later in B lymphocyte development. In this manner, long term lymphoid-cultured cells can be used to study the transitions that occur in VH repertoire expression which appear to be mediated by either B lymphocyte developmental microenvironment or population size

  9. Immune function assays as indicators of chromate exposure

    Energy Technology Data Exchange (ETDEWEB)

    Snyder, C.A.; Valle, C.D. (New York Univ. Medical Center, NY (United States))

    1991-05-01

    The potential immunomodulatory effects of chromium were investigated using a series of in vitro and in vivo studies. Chromium (as K{sub 2}CrO{sub 4}) in concentrations spanning five orders of magnitude was added in vitro to T-lymphocyte (concanavalin A) and B-lymphocyte (liposaccharide) mitogen cultures and was found to inhibit T-lymphocyte responses at all concentrations tested and to inhibit B-lymphocyte responses at all but the lowest concentration tested. When the same concentrations of chromium were employed in mixed lymphocyte cultures, antigen-induced thymidine uptake was inhibited at the highest concentrations, enhanced at 0.1 mg/L, and equal to control values at lower concentrations. Splenocytes isolated from rats exposed to K{sub 2}CrO{sub 4} in drinking water exhibited enhanced responses to T- and B-lymphocyte mitogens. The addition of 0.1 mg/L of chromium to a mixed lymphocyte culture containing splenocytes taken from chromium-exposed rats increased by 5-fold the uptake of thymidine by these cells. These increased responses of cells from chromium-exposed rats may indicate chromium-induced sensitization and may possibly be used as a biological marker for chromium exposure.

  10. Lymphocyte populations and apoptosis of peripheral blood B and T lymphocytes in children with end stage renal disease.

    Science.gov (United States)

    Saad, Khaled; Elsayh, Khalid I; Zahran, Asmaa M; Sobhy, Karema M

    2014-05-01

    End stage renal disease (ESRD) is a worldwide devastating health problem due to its increased prevalence in the population and high association with several pathologic conditions including immunodeficiency, which makes a significant contribution to morbidity and mortality. The present study aimed at analysis of T and B lymphocyte subpopulation and the detection of flowcytometric apoptosis markers on peripheral B and T lymphocytes in a cohort of children with ESRD. A case-control study was conducted on 28 children with ESRD. In addition, 30 age and sex matched healthy children were included as a control group. We used Annexin V-FITC binding assay as a sensitive probe for identifying cells undergoing apoptosis. Circulating neutrophils, T and B lymphocytes were lower in patient group. In addition, apoptotic B and T lymphocytes occurred more frequently in children with ESRD than in the control group. Our finding of low numbers of circulating neutrophils, T and B lymphocytes, and increased portion of apoptotic B and T lymphocytes in children with ESRD, may emphasize the fact that these derangements are the main mechanisms responsible for the impairment of the immune system in ESRD children, also it adds to the fact that both cellular and humoral immunity affected in ESRD children. Finally, uremia and increased peripheral lymphocyte apoptosis were the major causes of lymphocyte populations' depletion in our ESRD patients.

  11. Expression of BAFF and BR3 in patients with systemic lupus erythematosus

    Directory of Open Access Journals (Sweden)

    J.H. Duan

    2016-03-01

    Full Text Available The objective of this study was to examine the relationship between the expression of B cell activating factor (BAFF and BAFF receptor in patients with disease activity of systemic lupus erythematosus (SLE. Real-time RT-PCR was used to examine BAFF mRNA expression in peripheral blood monocytes of active and stable SLE patients and healthy controls. The percentage of BAFF receptor 3 (BR3 on B lymphocytes was measured by flow cytometry. Soluble BAFF levels in serum were assayed by ELISA. Microalbumin levels were assayed by an automatic immune analysis machine. BAFF mRNA and soluble BAFF levels were highest in the active SLE group, followed by the stable SLE group, and controls (P<0.01. The percentage of BR3 on B lymphocytes was downregulated in the active SLE group compared with the stable SLE group and controls (P<0.01. BAFF mRNA levels and soluble BAFF levels were higher in patients who were positive for proteinuria than in those who were negative (P<0.01. The percentage of BR3 on B lymphocytes was lower in patients who were positive for proteinuria than in those who were negative (P<0.01. The BAFF/BR3 axis may be over-activated in SLE patients. BAFF and BR3 levels may be useful parameters for evaluating treatment.

  12. Gut-Associated Lymphoid Tissue: A Key Tissue Inside the Mucosal Immune System of Hens Immunized with Escherichia coli F4

    Directory of Open Access Journals (Sweden)

    Maria F. Peralta

    2017-05-01

    Full Text Available Immunoglobulin Y (IgY is the predominant antibody found in hen’s (Gallus domesticus egg yolk. This antibody, developed against several microorganisms in hen egg yolk, has been successfully used as an alternative to immunoglobulins from mammals for use in immunodiagnostics and immunotherapy. Enteropathogenic Escherichia coli (E.coli F4 is the main etiological agent associated with swine neonatal diarrhea, and it causes notable economic losses in swine production. The aim of the present study was to evaluate the relationship between humoral immune response and the activation of gut-associated lymphoid tissue (GALT in laying hens intramuscularly immunized with E. coli F4. Adult laying Shaver hens were immunized with a bacterin based on an inactivated lysate E. coli F4 strain that was originally isolated from neonatal piglet diarrhea, following a recommended schedule. The percentage of B lymphocytes in blood and spleen homogenates was determined by flow cytometry. Villi histomorphometry and the size of germinal centers (GC activated in GALT and the spleen were measured in histological samples either stained with hematoxylin/eosin or through immunofluorescence. Antibody and isotype-specific antibodies in serum and egg yolk were measured using indirect enzyme-linked immunosorbent assay (ELISA. Secretory and serum immunoglobulin A (IgA were measured by ELISA tests. Laying hen with intramuscular immunization with E. coli F4 lysate, activated both mucosal and systemic protection. Mucosal protection was provided through B lymphocytes, and most of them were activated on Peyer’s patches and esophageal tonsils, in GALT. Furthermore, increased B lymphocyte number in the lamina propria of the gut, and increased intraepithelial plasmatic cell number, produced high levels of mucosal IgA. Activated B lymphocytes interacted with absorptive cells, immune cells, and microbiota in the gut, producing signals that were translated into a powerful physical defense by

  13. Gut-Associated Lymphoid Tissue: A Key Tissue Inside the Mucosal Immune System of Hens Immunized with Escherichia coli F4.

    Science.gov (United States)

    Peralta, Maria F; Magnoli, Alejandra; Alustiza, Fabrisio; Nilson, Armando; Miazzo, Raúl; Vivas, Adriana

    2017-01-01

    Immunoglobulin Y (IgY) is the predominant antibody found in hen's ( Gallus domesticus ) egg yolk. This antibody, developed against several microorganisms in hen egg yolk, has been successfully used as an alternative to immunoglobulins from mammals for use in immunodiagnostics and immunotherapy. Enteropathogenic Escherichia coli (E.coli) F 4 is the main etiological agent associated with swine neonatal diarrhea, and it causes notable economic losses in swine production. The aim of the present study was to evaluate the relationship between humoral immune response and the activation of gut-associated lymphoid tissue (GALT) in laying hens intramuscularly immunized with E. coli F 4 . Adult laying Shaver hens were immunized with a bacterin based on an inactivated lysate E. coli F 4 strain that was originally isolated from neonatal piglet diarrhea, following a recommended schedule. The percentage of B lymphocytes in blood and spleen homogenates was determined by flow cytometry. Villi histomorphometry and the size of germinal centers (GC) activated in GALT and the spleen were measured in histological samples either stained with hematoxylin/eosin or through immunofluorescence. Antibody and isotype-specific antibodies in serum and egg yolk were measured using indirect enzyme-linked immunosorbent assay (ELISA). Secretory and serum immunoglobulin A (IgA) were measured by ELISA tests. Laying hen with intramuscular immunization with E. coli F 4 lysate, activated both mucosal and systemic protection. Mucosal protection was provided through B lymphocytes, and most of them were activated on Peyer's patches and esophageal tonsils, in GALT. Furthermore, increased B lymphocyte number in the lamina propria of the gut, and increased intraepithelial plasmatic cell number, produced high levels of mucosal IgA. Activated B lymphocytes interacted with absorptive cells, immune cells, and microbiota in the gut, producing signals that were translated into a powerful physical defense by producing

  14. [Treatment of children with steroid-dependent nephrotic syndrome with rituximab].

    Science.gov (United States)

    Huang, Jianping; Du, Juan; Wang, Shuo; Xiao, Lili; Zhao, Xiaoyan

    2014-07-01

    To investigate the effects of rituximab (RTX) in children with steroid-dependent nephrotic syndrome. Five cases of children with steroid-dependent nephrotic syndrome seen from May 2012 to February 2013 in whom only steroid plus calcineurin inhibitor was effective and the disease recurred on reduction of dose were enrolled into this study, including 3 males and 2 females. Calcineurin inhibitors were stopped and steroids was changed to full dose. After the general condition improved, RTX was given at a dose of 375 mg/m(2), once a week for a total of three times for one course. After urine protein became negative for five days, the dose of steroid was changed to 2 mg/kg every other day, thereafter the dose was reduced by 5 mg per every 2 weeks, until discontinuation. After regular monitoring, when peripheral blood B cells were ≥ 3%, a second RTX was added. Urine protein was negative in 2-7 days in 5 patients after the first RTX treatment. Before treatment B lymphocytes in peripheral blood was 7.8% to 13.0% and after the first course of RTX treatment decreased to 0 in the first 6 to 8 months at the beginning of recovery, while in the first 7 to 10 months to 3.3%-6.1%, after a second RTX was given, B lymphocytes were reduced to 0, but in two cases (cases 1 and 3) B lymphocytes rose again at 16 and 17 months, in the first 17 and 18 months rose to 4.16% and 4.17%, RTX was given once again respectively. B lymphocytes were reduced to 0 again. Currently the 5 patients continued to be negative for urine protein, maintaining remission for 12 to 20 months.RTX infusion had no significant side effects, and side effects of steroid and calcineurin inhibitor disappeared. In children with steroid-dependent and only calcineurin inhibitor effective nephritic syndrome, relapse may still occur after improvement of nephrotic syndrome, after the first RTX treatment, regular monitoring of B lymphocytes, RTX supplementary treatment in advance can help discontinuation of steroids and

  15. Determination of normal expression patterns of CD86, CD210a, CD261, CD262, CD264, CD358, and CD361 in peripheral blood and bone marrow cells by flow cytometry.

    Science.gov (United States)

    Rudolf-Oliveira, Renata Cristina Messores; Auat, Mariangeles; Cardoso, Chandra Chiappin; Santos-Pirath, Iris Mattos; Lange, Barbara Gil; Pires-Silva, Jéssica; Moraes, Ana Carolina Rabello de; Dametto, Gisele Cristina; Pirolli, Mayara Marin; Colombo, Maria Daniela Holthausen Périco; Santos-Silva, Maria Claudia

    2018-02-01

    In 2010, new monoclonal antibodies were submitted to the 9th International Workshop on Human Leukocyte Differentiation Antigens, and there are few studies demonstrating normal expression patterns of these markers. Thus, the objective of this study was to determine the normal patterns of cell expression of CD86, CD210a, CD261, CD262, CD264, CD358, and CD361 in peripheral blood (PB) and bone marrow (BM) samples by flow cytometry. In the present study, CD86 was expressed only in monocytes and B lymphocytes in PB and in monocytes and plasma cells in BM. Regarding CD210a expression, in PB samples, monocytes and NK cells showed weak expression, while neutrophils, B and T lymphocytes, and basophils showed weak and partial expression. In BM samples, expression of CD210a was observed in eosinophils, monocytes, and B and T/NK lymphocytes. Weak expression of CD210a was also observed in neutrophilic cells and plasma cells. All B cell maturation stages had weak expression of CD210a except for immature B cells, which did not express this marker. In the present study, no cell type in PB samples showed positivity for CD261 and, in BM samples, there was very weak expression in neutrophilic series, monocytes, and B lymphocytes. Conversely, plasma cells showed positivity for CD261 with a homogeneous expression. For CD262, there was weak expression in monocytes, neutrophils, and B lymphocytes in PB samples and weak expression in monocytes, B lymphocytes, and plasma cells in BM samples. The evaluation of CD264 showed very weak expression in B cells in PB samples and no expression in BM cells. Very weak expression of CD358 was observed in neutrophils, monocytes, and B lymphocytes in PB and BM samples. In addition, in BM samples, plasma cells and T lymphocytes showed weak expression of CD358. In relation to the maturation stages of B cells, there was weak expression in pro-B cel, pre-B cell, and mature B cell. In the present study, it was possible to observe expression of CD361 in all

  16. CHARACTERISTICS OF TAND B-CELL SUBPOPULATION PROFILE IN THE PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE TREATED WITH VACCINE AGAINST PSEUDOMONAS AERUGINOSA

    Directory of Open Access Journals (Sweden)

    A. G. Borisov

    2015-01-01

    Full Text Available The aim of this study was to evaluate subpopulational profiles of Tand B-lymphocytes in the patients with chronic obstructive pulmonary disease (COPD under the influence of a multivalent vaccine against Pseudomonas pathogens, in order to justify its usage as a potential immune stimulator of microbial origin. Sixty patients (39 males and 21 females aged 40 – 58 years old with verified diagnosis of COPD II-III degree were included into the study group. All the patients received a standard COPD therapy. In accordance with planned treatment, this cohort was divided into two groups using a simple randomization. Group 1 included thirty COPD patients (20 men and 10 women who received standard treatment. Group 2 consisted of thirty COPD patients (19 men and 11 women who received treatment according to conventional schedule, but further, they were additionally treated with «Pseudovac» vaccine used as a infection-preventing measure. The «Pseudovac» vaccine was injected, according to appropriate instructions for the drug use. Immunological evaluation was performed three times: at admission, as well as 10 and 20 days of treatment. As a control group, 35 healthy individuals (19 men and 16 women of a similar age range have been examined. Assessment of Tand Bcellspecific immune phenotypes was determined by means of flow cytometry using direct immunofluorescence of leukocytes whole peripheral blood using specific monoclonal antibodies. We have found that Tand Blymphocyte profiles in the COPD patients are characterized by decreased numbers of T-cells (due to drop in cytotoxic T-cells, and increased B-lymphocyte contents. Relative amounts of NKTand γδT-lymphocytes showed an increase in cases of developing bacterial infection. The T-lymphocyte subpopulations in patients with COPD are characterized by increase in relative numbers of regulatory T-cells, Th2-lymphocytes, and T-cells expressing activation markers. B-lymphocyte population in COPD patients was

  17. Cancer causes increased mortality and is associated with altered apoptosis in murine sepsis.

    Science.gov (United States)

    Fox, Amy C; Robertson, Charles M; Belt, Brian; Clark, Andrew T; Chang, Katherine C; Leathersich, Ann M; Dominguez, Jessica A; Perrone, Erin E; Dunne, W Michael; Hotchkiss, Richard S; Buchman, Timothy G; Linehan, David C; Coopersmith, Craig M

    2010-03-01

    Whereas most septic patients have an underlying comorbidity, most animal models of sepsis use mice that were healthy before the onset of infection. Malignancy is the most common comorbidity associated with sepsis. The purpose of this study was to determine whether mice with cancer have a different response to sepsis than healthy animals. Prospective, randomized controlled study. Animal laboratory in a university medical center. C57Bl/6 mice. Animals received a subcutaneous injection of either 250,000 cells of the transplantable pancreatic adenocarcinoma cell line Pan02 (cancer) or phosphate-buffered saline (healthy). Three weeks later, mice given Pan02 cells had reproducible, nonmetastatic tumors. Both groups of mice then underwent intratracheal injection of either Pseudomonas aeruginosa (septic) or 0.9% NaCl (sham). Animals were killed 24 hrs postoperatively or followed-up 7 days for survival. Mice with cancer and healthy mice appeared similar when subjected to sham operation, although cancer animals had lower levels of T- and B-lymphocyte apoptosis. Septic mice with cancer had increased mortality compared to previously healthy septic mice subjected to the identical injury (52% vs. 28%; p = .04). This was associated with increased bacteremia but no difference in local pulmonary infection. Septic mice with cancer also had increased intestinal epithelial apoptosis. Although sepsis induced an increase in T- and B-lymphocyte apoptosis in all animals, septic mice with cancer had decreased T- and B-lymphocyte apoptosis compared to previously healthy septic mice. Serum and pulmonary cytokines, lung histology, complete blood counts, and intestinal proliferation were similar between septic mice with cancer and previously healthy septic mice. When subjected to the same septic insult, mice with cancer have increased mortality compared to previously healthy animals. Decreased systemic bacterial clearance and alterations in intestinal epithelial and lymphocyte apoptosis may

  18. Lack of galectin-3 disturbs mesenteric lymph node homeostasis and B cell niches in the course of Schistosoma mansoni infection.

    Science.gov (United States)

    Oliveira, Felipe L; Brand, Camila; Paula, Adelzon A; Arcanjo, Kátia D; Hsu, Daniel K; Liu, Fu-Tong; Takiya, Christina M; Borojevic, Radovan; Chammas, Roger; El-Cheikh, Márcia C

    2011-05-06

    Galectin-3 is a β-galactoside-binding protein that has been shown to regulate pathophysiological processes, including cellular activation, differentiation and apoptosis. Recently, we showed that galectin-3 acts as a potent inhibitor of B cell differentiation into plasma cells. Here, we have investigated whether galectin-3 interferes with the lymphoid organization of B cell compartments in mesenteric lymph nodes (MLNs) during chronic schistosomiasis, using WT and galectin-3(-/-) mice. Schistosoma mansoni synthesizes GalNAcβ1-4(Fucα1-3)GlcNAc(Lac-DiNAc) structures (N-acetylgalactosamine β1-4 N-acetylglucosamine), which are known to interact with galectin-3 and elicit an intense humoral response. Antigens derived from the eggs and adult worms are continuously drained to MLNs and induce a polyclonal B cell activation. In the present work, we observed that chronically-infected galectin-3(-/-) mice exhibited a significant reduced amount of macrophages and B lymphocytes followed by drastic histological changes in B lymphocyte and plasma cell niches in the MLNs. The lack of galectin-3 favored an increase in the lymphoid follicle number, but made follicular cells more susceptible to apoptotic stimuli. There were an excessive quantity of apoptotic bodies, higher number of annexin V(+)/PI(-) cells, and reduced clearance of follicular apoptotic cells in the course of schistosomiasis. Here, we observed that galectin-3 was expressed in non-lymphoid follicular cells and its absence was associated with severe damage to tissue architecture. Thus, we convey new information on the role of galectin-3 in regulation of histological events associated with B lymphocyte and plasma cell niches, apoptosis, phagocytosis and cell cycle properties in the MLNs of mice challenged with S.mansoni.

  19. Folate-deficiency induced cell-specific changes in the distribution of lymphocytes and granulocytes in rats.

    Science.gov (United States)

    Abe, Ikumi; Shirato, Ken; Hashizume, Yoko; Mitsuhashi, Ryosuke; Kobayashi, Ayumu; Shiono, Chikako; Sato, Shogo; Tachiyashiki, Kaoru; Imaizumi, Kazuhiko

    2013-01-01

    Folate (vitamin B(9)) plays key roles in cell growth and proliferation through regulating the synthesis and stabilization of DNA and RNA, and its deficiency leads to lymphocytopenia and granulocytopenia. However, precisely how folate deficiency affects the distribution of a variety of white blood cell subsets, including the minor population of basophils, and the cell specificity of the effects remain unclear. Therefore, we examined the effects of a folate-deficient diet on the circulating number of lymphocyte subsets [T-lymphocytes, B-lymphocytes, and natural killer (NK) cells] and granulocyte subsets (neutrophils, eosinophils, and basophils) in rats. Rats were divided into two groups, with one receiving the folate-deficient diet (FAD group) and the other a control diet (CON group). All rats were pair-fed for 8 weeks. Plasma folate level was dramatically lower in the FAD group than in the CON group, and the level of homocysteine in the plasma, a predictor of folate deficiency was significantly higher in the FAD group than in the CON group. The number of T-lymphocytes, B-lymphocytes, and NK cells was significantly lower in the FAD group than in the CON group by 0.73-, 0.49-, and 0.70-fold, respectively, indicating that B-lymphocytes are more sensitive to folate deficiency than the other lymphocyte subsets. As expected, the number of neutrophils and eosinophils was significantly lower in the FAD group than in the CON group. However, the number of basophils, the least common type of granulocyte, showed transiently an increasing tendency in the FAD group as compared with the CON group. These results suggest that folate deficiency induces lymphocytopenia and granulocytopenia in a cell-specific manner.

  20. Mucosal Immunity and B Cells in Teleosts: Effect of Vaccination and Stress.

    Science.gov (United States)

    Parra, David; Reyes-Lopez, Felipe E; Tort, Lluis

    2015-01-01

    Fish are subjected to several insults from the environment, which may endanger animal survival. Mucosal surfaces are the first line of defense against these threats, acting as a physical barrier to protect the animal but also functioning as an active immune tissue. Thus, four mucosal-associated lymphoid tissues (MALTs), which lead the immune responses in gut, skin, gills, and nose, have been described in fish. Humoral and cellular immunity, as well as their regulation and the factors that influence the response in these mucosal lymphoid tissues, are still not well known in most fish species. Mucosal B-lymphocytes and immunoglobulins (Igs) are key players in the immune response that takes place in those MALTs. The existence of IgT as a mucosal specialized Ig gives us the opportunity of measuring specific responses after infection or vaccination, a fact that was not possible until recently in most fish species. The vaccination process is influenced by several factors, being stress one of the main stimuli determining the success of the vaccine. Thus, one of the major goals in a vaccination process is to avoid possible situations of stress, which might interfere with fish immune performance. However, interaction between immune and neuroendocrine systems at mucosal tissues is still unknown. In this review, we will summarize the latest findings about B-lymphocytes and Igs in mucosal immunity and the effect of stress and vaccination on B-cell response at mucosal sites. It is important to point out that a limited number of studies have been published regarding stress in mucosa and very few about the influence of stress over mucosal B-lymphocytes.

  1. Mucosal immunity and B cells in teleosts: effect of vaccination and stress.

    Directory of Open Access Journals (Sweden)

    David eParra

    2015-07-01

    Full Text Available Fish are subjected to several insults from the environment, which may endanger animal survival. Mucosal surfaces are the first line of defense against those threats and they act as a physical barrier to protect the animal but also function as immunologically active tissues. Thus, four mucosal-associated lymphoid tissues have been described in fish, which lead the immune responses in gut, skin, gills and nose. Humoral and cellular immunity, as well as its regulation and the factors that influence the response in these mucosal lymphoid tissues is still not well known in most of fish species. Mucosal B-lymphocytes and immunoglobulins (Igs are one of the key players in the immune response after vaccination. Recent findings about IgT in trout have delimited the compartmentalization of immune response in systemic and mucosal. The existence of IgT as a specialized mucosa Ig gives us the opportunity of measuring mucosal specific responses after vaccination, a fact that was not possible until recently in most of the fish species. Vaccination process is influenced by several factors, being stress one of the main stimuli determining the success of the vaccine. Thus, one of the major goals in a vaccination process is to avoid possible situations of stress, which might interfere with fish immune performance. However, the interaction between immune and neuroendocrine systems at mucosal tissues is still unknown. In this review we will summarized the latest findings about B-lymphocytes and immunoglobulins in mucosal immunity and the effect of stress and vaccines on B cell response at mucosal sites. It is important to point out that a small number of studies have been published regarding mucosal stress and very few about the influence of stress over mucosal B-lymphocytes.

  2. Human BLyS facilitates engraftment of human PBL derived B cells in immunodeficient mice.

    Directory of Open Access Journals (Sweden)

    Madelyn R Schmidt

    2008-09-01

    Full Text Available The production of fully immunologically competent humanized mice engrafted with peripheral lymphocyte populations provides a model for in vivo testing of new vaccines, the durability of immunological memory and cancer therapies. This approach is limited, however, by the failure to efficiently engraft human B lymphocytes in immunodeficient mice. We hypothesized that this deficiency was due to the failure of the murine microenvironment to support human B cell survival. We report that while the human B lymphocyte survival factor, B lymphocyte stimulator (BLyS/BAFF enhances the survival of human B cells ex vivo, murine BLyS has no such protective effect. Although human B cells bound both human and murine BLyS, nuclear accumulation of NF-kappaB p52, an indication of the induction of a protective anti-apoptotic response, following stimulation with human BLyS was more robust than that induced with murine BLyS suggesting a fundamental disparity in BLyS receptor signaling. Efficient engraftment of both human B and T lymphocytes in NOD rag1(-/- Prf1(-/- immunodeficient mice treated with recombinant human BLyS is observed after adoptive transfer of human PBL relative to PBS treated controls. Human BLyS treated recipients had on average 40-fold higher levels of serum Ig than controls and mounted a de novo antibody response to the thymus-independent antigens in pneumovax vaccine. The data indicate that production of fully immunologically competent humanized mice from PBL can be markedly facilitated by providing human BLyS.

  3. Susceptibility of different leukocyte cell types to Vaccinia virus infection

    Directory of Open Access Journals (Sweden)

    Sánchez-Puig Juana M

    2004-11-01

    Full Text Available Abstract Background Vaccinia virus, the prototype member of the family Poxviridae, was used extensively in the past as the Smallpox vaccine, and is currently considered as a candidate vector for new recombinant vaccines. Vaccinia virus has a wide host range, and is known to infect cultures of a variety of cell lines of mammalian origin. However, little is known about the virus tropism in human leukocyte populations. We report here that various cell types within leukocyte populations have widely different susceptibility to infection with vaccinia virus. Results We have investigated the ability of vaccinia virus to infect human PBLs by using virus recombinants expressing green fluorescent protein (GFP, and monoclonal antibodies specific for PBL subpopulations. Flow cytometry allowed the identification of infected cells within the PBL mixture 1–5 hours after infection. Antibody labeling revealed that different cell populations had very different infection rates. Monocytes showed the highest percentage of infected cells, followed by B lymphocytes and NK cells. In contrast to those cell types, the rate of infection of T lymphocytes was low. Comparison of vaccinia virus strains WR and MVA showed that both strains infected efficiently the monocyte population, although producing different expression levels. Our results suggest that MVA was less efficient than WR in infecting NK cells and B lymphocytes. Overall, both WR and MVA consistently showed a strong preference for the infection of non-T cells. Conclusions When infecting fresh human PBL preparations, vaccinia virus showed a strong bias towards the infection of monocytes, followed by B lymphocytes and NK cells. In contrast, very poor infection of T lymphocytes was detected. These finding may have important implications both in our understanding of poxvirus pathogenesis and in the development of improved smallpox vaccines.

  4. SOME IMMUNOLOGICAL CHARACTERISTICS IN MUSTARD EXPOSED PATIENTS

    Directory of Open Access Journals (Sweden)

    M ADIB

    2001-06-01

    Full Text Available Introduction. Mutagenesis, carsinogenesis and cytotoxicity effects on body tissues are side effects of sulfur mustard which in turn, causes the bone marrow and lymphoid system dysfunction. Previous investigation in 31 Iranian chemical casualties, indicated the presence of persistant atypical lymphocytes and the decrease of T lymphocyte subsets and surface markers. The present study was performed to evaluate the changes of B lymphocyte surface markers in the above mentioned group and compare the changes with two other control groups. Methods.The first control group consisted of 30 chemical casaulities with the same clinical conditions and the same history of exposure to mustard but absence of atypical lymphocytes in their blood, and the second control group were consisted of 30 completely normal indivduals. Monoclonal antibodies congugated to fluoroscein isothiocyanate were used to determine B lymphocyte markers.The monoclonal antibodies used in this study were against human immunoglobuline δ and µ heavy chain, λ and κ light chains, anti human HLADR and anti human CD10. The tests were performed on 100 ml of peripheral blood, using flow cytometer model EPICS®XL. Results. In comparsion with normal controls, k and λ light chains showed a significant decrease (P < 0.001 while HLADR showed a significant increase (P < 0.001 in the two groups of poison gas injury. No significant difference could be seen in µ and δ chain. Two patients of victims group with atypical lymphocytes were CD10 positive. Discussion. Results of this investigation on B lymphocyte markers, suggests the increasing risk of neoplasuc or Iymphopro fife rative disorder with B cell origin, in chemical casaulties with mustard gas.

  5. Increased serum concentration of immune cell derived microparticles in polymyositis/dermatomyositis.

    Science.gov (United States)

    Baka, Zsuzsanna; Senolt, Ladislav; Vencovsky, Jiri; Mann, Herman; Simon, Piroska Sebestyén; Kittel, Agnes; Buzás, Edit; Nagy, György

    2010-02-16

    Microparticles are recently recognized players of intercellular communication. They are involved in signal transduction, cell activation and apoptosis. Their importance is also suggested in autoimmune diseases such as rheumatoid arthritis and systemic sclerosis. We investigated the role of microparticles in polymyositis/dermatomyositis, a group of rare autoimmune diseases, characterized by specific skin lesions and muscle weakness. The plasma concentration of monocyte and lymphocyte derived microparticles of 20 patients with polymyositis/dermatomyositis and 20 healthy controls were determined by flow cytometry. The structure of microparticles was visualized by electron microscopy. Significantly elevated numbers of monocyte (CD14 positive), T-lymphocyte (CD3 positive) and B-lymphocyte (CD19 positive) derived microparticles were found in the plasma samples of polymyositis/dermatomyositis patients, compared to healthy controls (p=0.001, 0.01 and 0.006, respectively). Furthermore, the plasma levels of monocyte and B-lymphocyte derived microparticles correlated with the manual muscle strength test (r=0.497, p=0.027; r=0.508, p=0.023; respectively). Patients with anti-Jo-1 antibody and lung involvement had significantly higher numbers of T- and B-lymphocyte and monocyte derived MPs (p=0.006, 0.012 and 0.007, respectively, for anti-Jo-1; p=0.013, 0.016 and 0.025, respectively, for lung involvement). After ultracentrifugation, CK activity could be detected only in traces in the resuspended pellet containing microparticles of healthy and diseased individuals. The electron microscopy revealed slightly different microparticles in the samples of patients with polymyositis/dermatomyositis. These results suggest that immune cell derived microparticles may contribute to the inflammatory process in polymyositis/dermatomyositis, however, CK-positive, possibly muscle derived microparticles do not seem to be present in the blood of patients with polymyositis

  6. X-linked agammaglobulinemia: Twenty years of single-center experience from North West India.

    Science.gov (United States)

    Singh, Surjit; Rawat, Amit; Suri, Deepti; Gupta, Anju; Garg, Ravinder; Saikia, Biman; Minz, Ranjana Walker; Sehgal, Shobha; Chan, Koon-Wing; Lau, Yu Lung; Kamae, Chikako; Honma, Kenichi; Nakagawa, Noriko; Imai, Kohsuke; Nonoyama, Shigeaki; Oshima, Koichi; Mitsuiki, Noriko; Ohara, Osamu

    2016-10-01

    X-linked agammaglobulinemia (XLA) is an X-linked genetic defect in maturation of B lymphocytes that results in the absence of B lymphocytes in the peripheral blood and profound hypogammaglobulinemia. It is caused by a mutation in the BTK gene located on the X chromosome. There are no large series describing XLA from the developing world. To analyze the clinical features, immunologic and genetic characteristics, and outcomes of 36 patients with XLA diagnosed and managed for a period of 2 decades. Diagnosis of XLA was made on the basis of presence of BTK gene mutation or marked reduction of B lymphocytes in peripheral blood with a family history of an affected male relative. The diagnosis was confirmed by genetic mutation studies in 28 patients with 25 unique mutations in the BTK gene. There was a significant delay in diagnosis in most of the patients. The mean (SD) delay in the diagnosis was 4.2 (3.5) years. Point mutations were the most common mutations detected, accounting for 68% of all mutations. Deletions and insertions were also seen in a few cases. Four of the mutations are novel mutations that have not been previously reported. Seven of the 36 patients (19%) were dead at the time of analysis in the present cohort. The mean survival was 137 months (95% confidence interval, 13-163 months). The present study is perhaps the largest series of patients with XLA from any developing country so far. Copyright © 2016 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  7. Erythema migrans: a reassessment of diagnostic criteria for early cutaneous manifestations of borreliosis with particular emphasis on clonality investigations.

    Science.gov (United States)

    Böer, A; Bresch, M; Dayrit, J; Falk, T M

    2007-06-01

    Controversy exists about the relationship of borrelia infection with B-cell lymphomas because B-cell clonality has been identified in infiltrates that contained borrelia-specific DNA. Systematic clinicopathological, immunophenotypical and molecular pathological studies of early borreliosis are lacking. (i) To clarify whether clonal B-cell populations are present already in early borreliosis of the skin (erythema migrans); (ii) to re-evaluate clinicopathological, immunophenotypical and molecular pathological criteria for diagnosis of erythema migrans. Study of 34 patients with erythema migrans confirmed by polymerase chain reaction (PCR). Infiltrates were analysed by histopathological and immunohistochemical methods and multiplex PCR for clonal IgH rearrangements. Erythema migrans shows a broad spectrum of changes including sparse infiltrates of T lymphocytes, dense interstitial granulomatous infiltrates (CD68+), and pseudolymphomatous patterns with germinal centre formation. There were accompanying epidermal changes in 59% of patients, and plasma cells were an inconsistent finding. B cells were few when infiltrates were sparse, but increased disproportionately when infiltrates were dense. IgH rearrangement studies revealed one pseudo-oligoclonal, three pseudoclonal and three clonal infiltrates. Pseudoclonality was encountered when infiltrates contained only few B lymphocytes. Infiltrates in erythema migrans are dominated by T cells followed by CD68+ histiocytes and B lymphocytes. Plasma cells are an inconsistent finding. Pseudoclonality of IgH rearrangement is a result of infiltrates being sparse in B lymphocytes and represents a pitfall in molecular pathological diagnosis that can only be avoided by duplicate or triplicate tests. Incidental B-cell clonality may be encountered in patients with unequivocal erythema migrans and should not be interpreted as a malignant lymphomatous process induced by borrelia.

  8. Lack of galectin-3 disturbs mesenteric lymph node homeostasis and B cell niches in the course of Schistosoma mansoni infection.

    Directory of Open Access Journals (Sweden)

    Felipe L Oliveira

    Full Text Available Galectin-3 is a β-galactoside-binding protein that has been shown to regulate pathophysiological processes, including cellular activation, differentiation and apoptosis. Recently, we showed that galectin-3 acts as a potent inhibitor of B cell differentiation into plasma cells. Here, we have investigated whether galectin-3 interferes with the lymphoid organization of B cell compartments in mesenteric lymph nodes (MLNs during chronic schistosomiasis, using WT and galectin-3(-/- mice. Schistosoma mansoni synthesizes GalNAcβ1-4(Fucα1-3GlcNAc(Lac-DiNAc structures (N-acetylgalactosamine β1-4 N-acetylglucosamine, which are known to interact with galectin-3 and elicit an intense humoral response. Antigens derived from the eggs and adult worms are continuously drained to MLNs and induce a polyclonal B cell activation. In the present work, we observed that chronically-infected galectin-3(-/- mice exhibited a significant reduced amount of macrophages and B lymphocytes followed by drastic histological changes in B lymphocyte and plasma cell niches in the MLNs. The lack of galectin-3 favored an increase in the lymphoid follicle number, but made follicular cells more susceptible to apoptotic stimuli. There were an excessive quantity of apoptotic bodies, higher number of annexin V(+/PI(- cells, and reduced clearance of follicular apoptotic cells in the course of schistosomiasis. Here, we observed that galectin-3 was expressed in non-lymphoid follicular cells and its absence was associated with severe damage to tissue architecture. Thus, we convey new information on the role of galectin-3 in regulation of histological events associated with B lymphocyte and plasma cell niches, apoptosis, phagocytosis and cell cycle properties in the MLNs of mice challenged with S.mansoni.

  9. Quantitation of antibody-secreting cells in the blood after vaccination with Haemophilus influenzae type b conjugate vaccine

    DEFF Research Database (Denmark)

    Barington, T; Heilmann, C; Andersen, V

    1990-01-01

    The human B-lymphocyte response to protein-conjugated polysaccharide antigens has not previously been studied at the cellular level. In order to do so, we developed and evaluated haemolytic plaque-forming cell assays detecting Haemophilus influenzae type b (Hib) capsular polysaccharide...... capsular polysaccharides from Hib and pneumococci. The predominance of IgA AbSC in response to both conjugate and pure polysaccharide vaccines is probably due to reactivation of the same clones of IgA-committed memory B cells originally primed at the mucosa by natural exposure to the polysaccharide...

  10. Cyclophosphamide 'pulses' in chronic progressive multiple sclerosis. A preliminary clinical trial.

    Science.gov (United States)

    Myers, L W; Fahey, J L; Moody, D J; Mickey, M R; Frane, M V; Ellison, G W

    1987-08-01

    To our knowledge, this is the first clinical trial in multiple sclerosis (MS) demonstrating the feasibility of directing immunomodulating therapy by monitoring immunologic results. Cyclophosphamide was administered at monthly intervals, escalating the dose until there was a significant reduction in both the number of blood B lymphocytes and helper/inducer (CD4) T cells of 14 patients with chronic progressive MS. The frequency and severity of adverse effects led us to conclude that the regimen is too toxic for the long-term treatment of patients with MS.

  11. ΔBAFF, an Alternate Splice Isoform That Regulates Receptor Binding and Biopresentation of the B Cell Survival Cytokine, BAFF*

    OpenAIRE

    Gavin, Amanda L; Aït-Azzouzene, Djemel; Ware, Carl F.; Nemazee, David

    2003-01-01

    The tumor necrosis family member BAFF is limiting for the survival of follicular B lymphocytes, but excessive BAFF signaling can lead to autoimmunity, suggesting that its activity must be tightly regulated. We have identified a conserved alternate splice isoform of BAFF, called ΔBAFF, which lacks 57 nt encoding the A–A1 loop and is co-expressed with BAFF in many mouse and human myeloid cells. Mouse ΔBAFF appears on the plasma membrane, but unlike BAFF it is inefficiently released by proteolys...

  12. Treatment of Graves' disease with rituximab specifically reduces the production of thyroid stimulating autoantibodies

    DEFF Research Database (Denmark)

    El Fassi, Daniel; Banga, J Paul; Gilbert, Jacqueline A

    2008-01-01

    Treatment of Graves' disease (GD) with the B-lymphocyte depleting agent rituximab in addition to standard methimazole-therapy prolongs remission. Paradoxically, it does not mediate a reduction in thyrotropin receptor antibody (TRAb) levels over that of methimazole monotherapy. Using a bioassay...... methimazole alone (p=0.04 between groups). The overall levels of TRAbs decreased by around 15% in both groups. Within one year of follow-up, rituximab therapy mediated specific decreases in thyroid-peroxidase antibody- and IgM levels, whereas IgG levels were unaffected. The data indicate that rituximab...

  13. [The time course of changes in cell immunological parameters during administration of live dry plague vaccine].

    Science.gov (United States)

    Bogacheva, N V; Darmov, I V; Borisevich, I V; Kriuchkov, A V; Pechenkin, D V

    2009-08-01

    The study of the time course of changes in cell immunological parameters by a magnetic separation technique in human beings during the administration of plague vaccine in relation to the immunological load revealed the higher blood levels of all T lymphocyte subpopulations on day 14 after vaccination. These changes are most typical of a primary vaccinated cohort. The increased frequency of plague vaccine administration and multiple immunizations with live plague, anthrax, and tularemia vaccines produce the time-course of changes in T lymphocyte populations (subpopulations) in response to the regular administration of plague vaccine. A high immunological load in man also promotes a significant reduction in the level of B lymphocytes.

  14. Specific blockade by CD54 and MHC II of CD40-mediated signaling for B cell proliferation and survival

    DEFF Research Database (Denmark)

    Doyle, I S; Hollmann, C A; Crispe, I N

    2001-01-01

    Regulation of B lymphocyte proliferation is critical to maintenance of self-tolerance, and intercellular interactions are likely to signal such regulation. Here, we show that coligation of either the adhesion molecule ICAM-1/CD54 or MHC II with CD40 inhibited cell cycle progression and promoted...... these effects. Addition of BCR or IL-4 signals did not overcome the effect of ICAM-1 or MHC II on CD40-induced proliferation. FasL expression was not detected in B cell populations. These results show that MHC II and ICAM-1 specifically modulate CD40-mediated signaling, so inhibiting proliferation...

  15. A method for autoradiographic studies of single clones of plaque forming cells

    International Nuclear Information System (INIS)

    Andersen, V.; Lefkovits, I.; Rigshospitalet, Copenhagen

    1977-01-01

    By limiting dilution of B lymphocytes from spleens of immunized mice, microcultures were obtained that contained only one clone of plaque forming cells (PFC). The cultured cells were labelled with [ 14 C]thymidine for varying period of time. Plaques were obtained in monolayers of sheep erythrocytes in plastic dishes. After fixation with glutaraldehyde, the bottoms of the dishes were stripped off and autoradiograms prepared. By this method, it is possible to determine the proportion of labelled PFC within a given clone and to quantitate the incorporation of label. The method described can be applied to study the incorporation of other labelled molecules and for cytochemical investigations

  16. Integration of Peptides into Organic Thin Film Transistor (OTFT)-based Printable Sensors

    Science.gov (United States)

    2017-02-10

    known as immunoglobulins , are produced by B lymphocytes and secreted into plasma [46]. They are Y shaped proteins that highly selectively bind to...molecules. There are also subclasses of immunoglobulin including IgA, IgD, IgE, IgG, and IgM which correspond to different heavy chain regions. The...6 8 10 200 300 400 500 600 No rm al ise d   Cu rre nt Time after Analyte Addition (s) A B 0 2 4 6 8 10 200 300 400 500 600 No rm al ise d   Cu rre nt

  17. A cAMP-Regulated Chloride Channel in Lymphocytes that is Affected in Cystic Fibrosis

    Science.gov (United States)

    Chen, Jennifer H.; Schulman, Howard; Gardner, Phyllis

    1989-02-01

    A defect in regulation of a chloride channel appears to be the molecular basis for cystic fibrosis (CF), a common lethal genetic disease. It is shown here that a chloride channel with kinetic and regulatory properties similar to those described for secretory epithelial cells is present in both T and B lymphocyte cell lines. The regulation of the channels by adenosine 3',5'-monophosphate (cAMP)--dependent protein kinase in transformed B cells from CF patients is defective. Thus, lymphocytes may be an accessible source of CF tissue for study of this defect, for cloning of the chloride channel complex, and for diagnosis of the disease.

  18. Ontogeny and characterization of blood leukocyte subsets and serum proteins in piglets before and after weaning

    DEFF Research Database (Denmark)

    Juul-Madsen, H.R.; Jensen, K.H.; Nielsen, Jens

    2010-01-01

    cytometry using monoclonal antibodies against CD1, CD3, CD4, CD8a CD14, CD21, CD172 (SWC3a), CD284 (TLR4), SLAI, and SLAII were performed to identify T-lymphocyte subsets, B-lymphocytes, monocytes, and granulocytes. ELISA was used to measure the concentration of serum proteins. Several of the analyzed......Existing knowledge about the development of the porcine immune system was extended by phenotypic characterization of leukocyte subsets and with assessment of Mannan-Binding Lectin (MBL) and immunoglobulin concentrations in peripheral blood of healthy piglets. Single-color and/or double-color flow...

  19. Indikationer for radioimmunterapi til patienter med non-Hodgkins lymfom

    DEFF Research Database (Denmark)

    Frølund, Ulf Christian; Hansen, Per Boye

    2011-01-01

    Radioimmunotherapy is a well-known treatment for non-Hodgkin's lymphoma. (90)yttrium (Y)-ibritumomab-tiuxetan consists of a radioisotope conjugated to a monoclonal anti-cluster of differentiation 20 antibody, which is targeted against B-lymphocytes. Initially the treatment indication was relapse...... of low-grade non-Hodgkin's lymphoma. However, (90)Y-ibritumomab-tiuxetan has later been used in clinical trials in the treatment of other types of non-Hodgkin's lymphoma and prior to stem cell transplantation. Based on the literature this systematic review aims to throw light on the future possibilities...

  20. Structure of an Ebf1:DNA complex reveals unusual DNA recognition and structural homology with Rel proteins

    OpenAIRE

    Treiber, Nora; Treiber, Thomas; Zocher, Georg; Grosschedl, Rudolf

    2010-01-01

    Early B-cell factor 1 (Ebf1) is a key transcriptional determinant of B-lymphocyte differentiation whose DNA-binding domain has no sequence similarity to other transcription factor families. Here we report the crystal structure of an Ebf1 dimer bound to its palindromic recognition site. The DNA-binding domain adopts a pseudoimmunoglobulin-like fold with novel topology, but is structurally similar to the Rel homology domains of NFAT and NF-κB. Ebf1 contacts the DNA with two loop-based modules a...

  1. The Ebf1 knockout mouse and glomerular maturation.

    Science.gov (United States)

    Schmidt-Ott, Kai M

    2014-05-01

    Mice deficient in the transcription factor early B-cell factor 1 (Ebf1) lack mature B lymphocytes but have additional phenotypes suggesting functions outside the hematopoietic system. Fretz et al. report that these mice also exhibit quantitative and qualitative developmental renal defects and develop progressive podocyte foot process effacement. The findings not only suggest that Ebf1 may be pivotal to the transcriptional podocyte network, but also illustrate the importance of distinguishing cell-autonomous and non-autonomous inputs to podocyte maturation and integrity.

  2. Research advances in immune tolerance in chronic hepatitis B virus infection

    Directory of Open Access Journals (Sweden)

    WU Fengping

    2017-05-01

    Full Text Available Immune tolerance refers to the specific non-response or negative response of T and B lymphocytes to antigens. According to the period of formation, immune tolerance can be classified into central tolerance and peripheral tolerance. Immune tolerance to hepatitis B virus (HBV after HBV infection is considered a major cause of chronic HBV infection. This article briefly reviews the roles of HBeAg, functional defects of dendritic cells, low response of cytotoxic T lymphocytes, T helper cells and cytokines, variations of HBV genotype and genome, and host gene polymorphisms in the development of immune tolerance in chronic HBV infection, as well as related research advances.

  3. Gastric adenocarcinoma in a patient with X-linked agammaglobulinemia and HIV: Case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Joud Hajjar

    2016-09-01

    Full Text Available X-linked agammaglobulinemia (XLA is an X-linked inherited disease usually caused by a germline mutation in the BTK gene leading to Bruton’s tyrosine kinase deficiency, which results in the impaired development of B-lymphocytes and a subsequent lack of immunoglobulin production. Patients with XLA have an increased susceptibility to bacterial and viral infections, and multiple case reports have been published regarding an association between XLA and gastrointestinal (GI malignancy. Here, we describe a case of a 25-year-old man with XLA and HIV, who developed gastric adenocarcinoma. Previously reported cases of XLA and GI malignancy are also reviewed and summarized.

  4. Repair of U/G and U/A in DNA by UNG2-associated repair complexes takes place predominantly by short-patch repair both in proliferating and growth-arrested cells

    DEFF Research Database (Denmark)

    Akbari, Mansour; Otterlei, Marit; Pena Diaz, Javier

    2004-01-01

    Nuclear uracil-DNA glycosylase UNG2 has an established role in repair of U/A pairs resulting from misincorporation of dUMP during replication. In antigen-stimulated B-lymphocytes UNG2 removes uracil from U/G mispairs as part of somatic hypermutation and class switch recombination processes. Using......, PCNA and DNA ligase, the latter detected as activity. Short-patch repair was the predominant mechanism both in extracts and UNG2-ARC from proliferating and less BER-proficient growth-arrested cells. Repair of U/G mispairs and U/A pairs was completely inhibited by neutralizing UNG...

  5. Mono- and dual-targeting triplebodies activate natural killer cells and have anti-tumor activity in vitro and in vivo against chronic lymphocytic leukemia

    OpenAIRE

    Vyas, Maulik; Schneider, Ann-Charlott; Shatnyeva, Olga; Reiners, Katrin S.; Tawadros, Samir; Kloess, Stephan; K?hl, Ulrike; Hallek, Michael; Hansen, Hinrich P.; Pogge von Strandmann, Elke

    2016-01-01

    Chronic lymphocytic leukemia (CLL) is the most common form of leukemia that affects B lymphocytes in adults. Natural killer (NK) cells in CLL patients are intrinsically potent but display poor in situ effector functions. NKG2D is an activating receptor found on NK and CD8+ T cells and plays a role in immunosurveillance of CLL. In this study, we developed mono- and dual-targeting triplebodies utilizing a natural ligand for human NKG2D receptor (ULBP2) to retarget NK cells against tumor cells. ...

  6. Study on serum TNF-α level, B-cell count and T-cell subsets distribution in peripheral blood in patients with rheumatoid arthritis

    International Nuclear Information System (INIS)

    Shi Buqing

    2006-01-01

    Objective: To study the changes of serum TNF-α levels, B-cell count and T-cell subsets distribution in peripheral blood in patients with rheumatoid arthritis. Methods: Serum TNF-α levels (with RIA), B cell as well as T cell subsets distribution type (with monoclonal antibody technique) were examined in 37 patients with rheumatoid arthritis and 30 controls. Results Serum TNF-α levels and B lymphocytes count were significantly higher in the patients than those in controls (P 3 , CD 4 and CD 4 /CD 8 were obviously lower (P<0.01). Conclusion: Rheumatoid arthritis is an autoimmune disease with abnormal immunoregulation. (authors)

  7. Phenotypic characterisation of immune cell infiltrates in testicular germ cell neoplasia

    DEFF Research Database (Denmark)

    Hvarness, Tine; Nielsen, John E; Almstrup, Kristian

    2013-01-01

    and overt seminoma, in comparison to biopsies from infertile men without neoplasia. The composition of immune cells was similar across all the groups studied. Macrophages, CD8(+) and CD45R0(+) T lymphocytes constituted the majority of infiltrates, B lymphocytes were present in an intermediate proportion...... and very few CD4(+) and FoxP3(+) T cells were detected. HLA-I antigen was more abundant in Sertoli cells in tubules containing CIS than in those with normal spermatogenesis. This study showed a phenotypically comparable composition of infiltrating immune cells independently of the presence of neoplasia...

  8. Medfødt immunitet, autoimmunitet og autoinflammation

    DEFF Research Database (Denmark)

    Bendtzen, Klaus

    2011-01-01

    -like receptors (NLR). These signals include nuclear fragments released by stressed or dying cells. NLR-signalling activates the enzyme caspase-1, which is required for release of pro-inflammatory cytokines such as interleukin (IL)-1ß, IL-18 and IL-33. Dysfunction of innate immunity is central to autoinflammation......T and B lymphocytes of the acquired immune system are functionally superimposed on the evolutionary old innate immune system. The latter recognizes conserved microbial structures through pattern recognition receptors (PRR) which are coactivated by "danger" signals through cytoplasmic PRR termed NOD...

  9. Polycyclic’ Aromatic Hydrocarbon Induced Intracellular Signaling and Lymphocyte Apoptosis

    DEFF Research Database (Denmark)

    Schneider, Alexander M.

    lymphocytes. Our experiments on preB lymphocytes supported by stromal cells suggest that apoptosis is one of the mechanisms for PAH immunosuppression. It could be either due to direct effect of the PAH on the B cells, via stromal cell signaling. Ubiquitous PAH-like toxin, fluoranthene, was tested for it......’s ability to initiate apoptosis in T cell hybridomas. Our data demonstrate that PAH may induce apoptosis and innnunotoxicity in T cell branch of immune system. The mechanism of this process seems to be the AhR independent, and mediated by Ca...

  10. Current status of pig heart xenotransplantation.

    Science.gov (United States)

    Mohiuddin, Muhammad M; Reichart, Bruno; Byrne, Guerard W; McGregor, Christopher G A

    2015-11-01

    Significant progress in understanding and overcoming cardiac xenograft rejection using a clinically relevant large animal pig-to-baboon model has accelerated in recent years. This advancement is based on improved immune suppression, which attained more effective regulation of B lymphocytes and possibly newer donor genetics. These improvements have enhanced heterotopic cardiac xenograft survival from a few weeks to over 2 years, achieved intrathoracic heterotopic cardiac xenograft survival of 50 days and orthotopic survival of 57 days. This encouraging progress has rekindled interest in xenotransplantation research and refocused efforts on preclinical orthotopic cardiac xenotransplantation. Copyright © 2015 IJS Publishing Group Limited. All rights reserved.

  11. The Shc Family Protein Adaptor, Rai, Negatively Regulates T Cell Antigen Receptor Signaling by Inhibiting ZAP-70 Recruitment and Activation

    OpenAIRE

    Ferro, Micol; Savino, Maria Teresa; Ortensi, Barbara; Finetti, Francesca; Genovese, Luca; Masi, Giulia; Ulivieri, Cristina; Benati, Daniela; Pelicci, Giuliana; Baldari, Cosima T.

    2011-01-01

    Rai/ShcC is a member of the Shc family of protein adaptors expressed with the highest abundance in the central nervous system, where it exerts a protective function by coupling neurotrophic receptors to the PI3K/Akt survival pathway. Rai is also expressed, albeit at lower levels, in other cell types, including T and B lymphocytes. We have previously reported that in these cells Rai attenuates antigen receptor signaling, thereby impairing not only cell proliferation but also, opposite to neuro...

  12. Neuritis of the cauda equina in a dog.

    Science.gov (United States)

    Saey, V; Martlé, V; Van Ham, L; Chiers, Koen

    2010-10-01

    This study presents the first case report of neuritis of the cauda equina in a dog, including characterisation of the inflammatory infiltrate. The dog in question, a 6-year-old Welsh springer spaniel, was presented with flaccid tail and faecal and urinary incontinence. The histological lesions included severe mononuclear cell infiltration of the nerve roots of the cauda equina and of the lumbar nerve roots. The infiltrate was composed of large numbers of T-lymphocytes and B-lymphocytes and small numbers of macrophages. Polymerase chain reactions of brain and spinal tissues were positive for Neospora caninum. © 2010 British Small Animal Veterinary Association.

  13. Exceptional Antibodies Produced by Successive Immunizations.

    Directory of Open Access Journals (Sweden)

    Patricia J Gearhart

    2015-12-01

    Full Text Available Antibodies stand between us and pathogens. Viruses mutate quickly to avoid detection, and antibodies mutate at similar rates to hunt them down. This death spiral is fueled by specialized proteins and error-prone polymerases that change DNA sequences. Here, we explore how B lymphocytes stay in the race by expressing activation-induced deaminase, which unleashes a tsunami of mutations in the immunoglobulin loci. This produces random DNA substitutions, followed by selection for the highest affinity antibodies. We may be able to manipulate the process to produce better antibodies by expanding the repertoire of specific B cells through successive vaccinations.

  14. Radiation versus immunity in early breast cancer

    International Nuclear Information System (INIS)

    Turnbull, A.R.; Turner, D.T.L.; Jones, B.M.; Wright, R.

    1979-01-01

    Comparison of various in-vitro immunological tests has been made in patients with early breast cancer undergoing simple mastectomy alone or simple mastectomy with additional radical radiotherapy to the chest wall and regional lymphatics. Radiotherapy caused a depletion of both T and B lymphocytes in the peripheral blood, but did not substantially alter the proportions of these two cell populations. The response to certain mitogens was also depressed for at least 12 months, but the sensitivity of the leucocytes to tumour antigens in the leucocyte migration inhibition test was preserved, following irradiation. (author)

  15. Cell-mediated and humoral immunity in west syndrome

    Directory of Open Access Journals (Sweden)

    Terezinha C. B. Montelli

    1981-03-01

    Full Text Available The immunological status of five children with West syndrome consequent to previous cerebral lesions was investigated. Three children had West syndrome and two were in transition from West to Lennox-Gastaut syndrome. All of them showed cellular immunological deficiencies in the following tests: sensitization to DNCB, intracutaneous reaction to PHA, inhibition of leucocyte migration, blastic transformation of lymphocytes, T and B lymphocytes in peripheric blood and levels of serum immunoglobulins. These immunological deficiencies, of different degrees of severity, were associated to frequent infections in these children. A possible association between the immunological deficiencies and autoimmunity is discussed.

  16. Human milk-derived B cells: a highly activated switched memory cell population primed to secrete antibodies.

    Science.gov (United States)

    Tuaillon, Edouard; Valea, Diane; Becquart, Pierre; Al Tabaa, Yassine; Meda, Nicolas; Bollore, Karine; Van de Perre, Philippe; Vendrell, Jean-Pierre

    2009-06-01

    While secretory Abs have been extensively explored in human breast milk, the existence, features, and functions of B lymphocytes remain largely unexplored in this compartment. We analyzed breast milk and blood lymphocytes from 21 lactating women, including 12 HIV-1-infected mothers. Breast milk B cells displayed a phenotype of class-switched memory B cells, with few IgD(+) memory and naive B cells. We observed that breast milk B lymphocytes bore a unique profile of adhesion molecules (CD44(+), CD62L(-), alpha(4)beta(7)(+/-), alpha(4)beta(1)(+)). Higher percentages of activated B cells (CD38(+)), large-sized B cells, plasmablasts, and plasma cells (CD19(+), CD20(low/-), CD27(high), CD138(+)) were found as compared with blood. This indicates that a significant proportion of breast milk B cells underwent terminal plasma cell differentiation. We also observed a higher frequency of cells secreting Ig spontaneously in breast milk. Among these cells, IgG-secreting cells predominated over IgA-secreting cells as measured by Ig ELISPOT assays. Specific Ab-secreting cells were investigated following polyclonal activation using the CD40L ligation. Finally, the detection of anti-HIV-1-secreting cells demonstrates the existence of B cells specific to HIV-1 Ag in breast milk from HIV-1-infected women. Breast milk B cells display a phenotype strikingly different from blood, are primed to secrete Abs, and have a mucosal homing profile similar to B cells located in gut-associated lymphoid tissue.

  17. Neurophysiological and clinical responses to rituximab in patients with anti-MAG polyneuropathy.

    Science.gov (United States)

    Zara, Gabriella; Zambello, Renato; Ermani, M

    2011-12-01

    Rituximab treatment has shown clinical improvement in anti-myelin associated glycoprotein (MAG) polyneuropathy. We analyzed scores of clinical scales and the most sensitive electrophysiological parameters before and after immunomodulating treatment with rituximab in a group of patients affected by anti-MAG demyelinating polyneuropathy. Clinical scores, the percentage of CD20 B-lymphocytes, anti-MAG antibody titers and electrophysiological data in 7 patients with anti-MAG polyneuropathy were analyzed. The patients were examined before a cycle with rituximab, 6, 12 and 24 months after the end of the treatment. Two patients were treated with rituximab additional cycles and re-evaluated 48 months after the first treatment. There were no evident correlation between anti-MAG serum antibody titers or clinical scales and electrodiagnostic data. Significant decrease in the proportion of CD20 B-lymphocytes was observed. Significant anti-MAG antibodies titers reduction was detected after re-treatment. At follow-up, pinprik sensation and two point discrimination presented a significant improvement compared with the score before treatment. In our patients, rituximab did not improve any electrophysiological data. No correlation with anti-MAG serum antibodies course was found. With rituximab only pin sensibility improved. Rituximab re-treatment significantly reduces anti-MAG serum antibodies titers but improves only small fibers sensibility. Copyright © 2011 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  18. Inhibition of GLI, but not Smoothened, induces apoptosis in chronic lymphocytic leukemia cells.

    Science.gov (United States)

    Desch, P; Asslaber, D; Kern, D; Schnidar, H; Mangelberger, D; Alinger, B; Stoecher, M; Hofbauer, S W; Neureiter, D; Tinhofer, I; Aberger, F; Hartmann, T N; Greil, R

    2010-09-02

    The Hedgehog (Hh) pathway regulates cell proliferation and survival and contributes to tumorigenesis. We investigated the expression and function of this pathway in B-cell chronic lymphocytic leukemia (CLL) cells and in healthy B lymphocytes. Profiling of cognate Hh pathway members revealed reduced expression of two key Hh signaling effectors, Smoothened (SMOH) and GLI, in CLL cells, whereas transcription levels of other investigated members resembled normal B-lymphocyte levels. Examining the functional role of SMOH and GLI in cell survival, we found that CLL cells were hardly sensitive toward specific SMOH inhibition, but showed an unspecific decline in cell viability in response to high concentrations of the SMOH antagonist cyclopamine. In contrast, treatment with the novel GLI antagonist GANT61 reduced expression of the target gene Patched and preferentially decreased the viability of malignant cells. Specific RNA interference knockdown experiments in a CLL-derived cell line confirmed the autonomous role of GLI in malignant cell survival. GANT61-induced apoptosis in primary leukemic cells was partly attenuated by protective stromal cells, but not soluble sonic hedgehog ligand. In summary, our data show a downregulation of the classical Hh pathway in CLL and suggest an intrinsic SMOH-independent role of GLI in the ex vivo survival of CLL cells.

  19. Strategies to Obtain Diverse and Specific Human Monoclonal Antibodies From Transgenic Animals.

    Science.gov (United States)

    Brüggemann, Marianne; Osborn, Michael J; Ma, Biao; Buelow, Roland

    2017-08-01

    Techniques to obtain large quantities of antigen-specific monoclonal antibodies (mAbs) were first established in the 1970s when Georges Köhler and César Milstein immortalized antibody-producing mouse B-lymphocytes by fusion with myeloma cells (http://www.whatisbiotechnology.org/exhibitions/milstein). Combined with the expression of human antibodies in transgenic animals, this technique allowed upon immunization the generation of highly specific fully human mAbs for therapeutic applications. Apart from being extremely beneficial, mAbs are a huge success commercially. However, despite cell fusion generating many useful mAbs questions have been asked about which types of cells are prone to fuse and whether other methods may identify a wider range of binders. The discovery that expression libraries, using Escherichia coli or yeast, produced different specificities was intriguing and more recently Next-Generation Sequencing has identified wide-ranging usage with highly diverse and unique repertoires. Another strategy is the combination of flow cytometry sorting of antigen-binding B lymphocytes and single-cell reverse transcription polymerase chain reaction followed by reexpression, which has identified many high-affinity mAbs.

  20. [Octarphin--Nonopioid Peptide of the Opioid Origin].

    Science.gov (United States)

    Navolotskaya, E V

    2015-01-01

    The data on the properties and mechanism of action of the peptide octarphin (TPLVTLFK, the fragment 12-19 of β-endorphin)--a selective agonist of nonopioid (insensitive to the action of the opioid antagonist naloxone) β-endorphin receptor found on n immune cells (peritoneal macrophages, T and B lymphocytes of spleen and blood), endocrine (adrenal cortex, hypothalamus), cardiovascular (cardiomyocytes) systems are analyzed and systematized. Binding to the receptor octarphin increases increases the mitogen-induced pro- liferation of human and mouse T and B lymphocytes in vitro, activates murine peritoneal macrophages in vitro and in vivo, stimulates growth of human T-lymphoblast cell lines Jurkat and MT-4, inhibits adenylate cyclase activity of rat adrenal cortex membranes and suppresses the secretion of glucocorticoids from the adrenal gland into the blood. It was shown that in a concentration range of 1-1000 nM the peptide increases the activity of inducible NO-synthase (iNOS), and the content of NO and cGMP in lipopolysaccharide-activated murine peritoneal macrophages. Taking into account that NO acts as a primary activator of soluble guanylate cyclase (sGC), it can be assumed that the activating effect of octarphin on macrophages is realized in the following way: increase in th iNOS expression --> increase in the NO production --> increase in the sGC activity --> increase in intracellular levels of cGMP.

  1. Histological Lesions and Cellular Response in the Skin of Alpine Chamois (Rupicapra r. rupicapra Spontaneously Affected by Sarcoptic Mange

    Directory of Open Access Journals (Sweden)

    Claudia Salvadori

    2016-01-01

    Full Text Available Population dynamics of chamois (genus Rupicapra, subfamily Caprinae can be influenced by infectious diseases epizootics, of which sarcoptic mange is probably the most severe in the Alpine chamois (Rupicapra rupicapra rupicapra. In this study, skin lesions and cellular inflammatory infiltrates were characterized in 44 Alpine chamois affected by sarcoptic mange. Dermal cellular responses were evaluated in comparison with chamois affected by trombiculosis and controls. In both sarcoptic mange and trombiculosis, a significantly increase of eosinophils, mast cells, T and B lymphocytes, and macrophages was detected. Moreover, in sarcoptic mange significant higher numbers of T lymphocytes and macrophages compared to trombiculosis were observed. Lesions in sarcoptic mange were classified in three grades, according to crusts thickness, correlated with mite counts. Grade 3 represented the most severe form with crust thickness more than 3.5 mm, high number of mites, and severe parakeratosis with diffuse bacteria. Evidence of immediate and delayed hypersensitivity was detected in all three forms associated with diffuse severe epidermal hyperplasia. In grade 3, a significant increase of B lymphocytes was evident compared to grades 1 and 2, while eosinophil counts were significantly higher than in grade 1, but lower than in grade 2 lesions. An involvement of nonprotective Th2 immune response could in part account for severe lesions of grade 3.

  2. Histological Lesions and Cellular Response in the Skin of Alpine Chamois (Rupicapra r. rupicapra) Spontaneously Affected by Sarcoptic Mange.

    Science.gov (United States)

    Salvadori, Claudia; Rocchigiani, Guido; Lazzarotti, Camilla; Formenti, Nicoletta; Trogu, Tiziana; Lanfranchi, Paolo; Zanardello, Claudia; Citterio, Carlo; Poli, Alessandro

    2016-01-01

    Population dynamics of chamois (genus Rupicapra, subfamily Caprinae) can be influenced by infectious diseases epizootics, of which sarcoptic mange is probably the most severe in the Alpine chamois (Rupicapra rupicapra rupicapra). In this study, skin lesions and cellular inflammatory infiltrates were characterized in 44 Alpine chamois affected by sarcoptic mange. Dermal cellular responses were evaluated in comparison with chamois affected by trombiculosis and controls. In both sarcoptic mange and trombiculosis, a significantly increase of eosinophils, mast cells, T and B lymphocytes, and macrophages was detected. Moreover, in sarcoptic mange significant higher numbers of T lymphocytes and macrophages compared to trombiculosis were observed. Lesions in sarcoptic mange were classified in three grades, according to crusts thickness, correlated with mite counts. Grade 3 represented the most severe form with crust thickness more than 3.5 mm, high number of mites, and severe parakeratosis with diffuse bacteria. Evidence of immediate and delayed hypersensitivity was detected in all three forms associated with diffuse severe epidermal hyperplasia. In grade 3, a significant increase of B lymphocytes was evident compared to grades 1 and 2, while eosinophil counts were significantly higher than in grade 1, but lower than in grade 2 lesions. An involvement of nonprotective Th2 immune response could in part account for severe lesions of grade 3.

  3. Antibodies That Block or Activate Mouse B Cell Activating Factor of the Tumor Necrosis Factor (TNF) Family (BAFF), Respectively, Induce B Cell Depletion or B Cell Hyperplasia*

    Science.gov (United States)

    Kowalczyk-Quintas, Christine; Schuepbach-Mallepell, Sonia; Vigolo, Michele; Willen, Laure; Tardivel, Aubry; Smulski, Cristian R.; Zheng, Timothy S.; Gommerman, Jennifer; Hess, Henry; Gottenberg, Jacques-Eric; Mackay, Fabienne; Donzé, Olivier

    2016-01-01

    B cell activating factor of the TNF family (BAFF), also known as B lymphocyte stimulator, is a ligand required for the generation and maintenance of B lymphocytes. In this study, the ability of different monoclonal antibodies to recognize, inhibit, or activate mouse BAFF was investigated. One of them, a mouse IgG1 named Sandy-2, prevented the binding of BAFF to all of its receptors, BAFF receptor, transmembrane activator and calcium modulating ligand interactor, and B cell maturation antigen, at a stoichiometric ratio; blocked the activity of mouse BAFF on a variety of cell-based reporter assays; and antagonized the prosurvival action of BAFF on primary mouse B cells in vitro. A single administration of Sandy-2 in mice induced B cell depletion within 2 weeks, down to levels close to those observed in BAFF-deficient mice. This depletion could then be maintained with a chronic treatment. Sandy-2 and a previously described rat IgG1 antibody, 5A8, also formed a pair suitable for the sensitive detection of endogenous circulating BAFF by ELISA or using a homogenous assay. Interestingly, 5A8 and Sandy-5 displayed activities opposite to that of Sandy-2 by stimulating recombinant BAFF in vitro and endogenous BAFF in vivo. These tools will prove useful for the detection and functional manipulation of endogenous mouse BAFF and provide an alternative to the widely used BAFF receptor-Fc decoy receptor for the specific depletion of BAFF in mice. PMID:27451394

  4. Characterization of cDNA for human tripeptidyl peptidase II: The N-terminal part of the enzyme is similar to subtilisin

    International Nuclear Information System (INIS)

    Tomkinson, B.; Jonsson, A-K

    1991-01-01

    Tripeptidyl peptidase II is a high molecular weight serine exopeptidase, which has been purified from rat liver and human erythrocytes. Four clones, representing 4453 bp, or 90% of the mRNA of the human enzyme, have been isolated from two different cDNA libraries. One clone, designated A2, was obtained after screening a human B-lymphocyte cDNA library with a degenerated oligonucleotide mixture. The B-lymphocyte cDNA library, obtained from human fibroblasts, were rescreened with a 147 bp fragment from the 5' part of the A2 clone, whereby three different overlapping cDNA clones could be isolated. The deduced amino acid sequence, 1196 amino acid residues, corresponding to the longest open rading frame of the assembled nucleotide sequence, was compared to sequences of current databases. This revealed a 56% similarity between the bacterial enzyme subtilisin and the N-terminal part of tripeptidyl peptidase II. The enzyme was found to be represented by two different mRNAs of 4.2 and 5.0 kilobases, respectively, which probably result from the utilziation of two different polyadenylation sites. Futhermore, cDNA corresponding to both the N-terminal and C-terminal part of tripeptidyl peptidase II hybridized with genomic DNA from mouse, horse, calf, and hen, even under fairly high stringency conditions, indicating that tripeptidyl peptidase II is highly conserved

  5. Atypical X-linked agammaglobulinaemia caused by a novel BTK mutation in a selective immunoglobulin M deficiency patient.

    Science.gov (United States)

    Lim, Lee-Moay; Chang, Jer-Ming; Wang, I-Fang; Chang, Wei-Chiao; Hwang, Daw-Yang; Chen, Hung-Chun

    2013-09-27

    X-linked agammaglobulinaemia (XLA) is the most common inherited humoural immunodeficiency disorder. Mutations in the gene coding for Bruton's tyrosine kinase (BTK) have been identified as the cause of XLA. Most affected patients exhibit a marked reduction of serum immunoglobulins, mature B cells, and an increased susceptibility to recurrent bacterial infections. However, the diagnosis of XLA can be a challenge in certain patients who have near-normal levels of serum immunoglobulin. Furthermore, reports on XLA with renal involvement are scant. We report an atypical XLA patient who presented with selective immunoglobulin M (IgM) immunodeficiency and nephropathy. He was diagnosed with selective IgM immunodeficiency, based on his normal serum immunoglobulin G (IgG) and immunoglobulin A (IgA) levels but undetectable serum IgM level. Intravenous immunoglobulin was initiated due to increased infections and persistent proteinuria but no improvement in proteinuria was found. A lupus-like nephritis was detected in his kidney biopsy and the proteinuria subsided after receiving a mycophenolate mofetil regimen. Although he had a history of recurrent bacterial infections since childhood, XLA was not diagnosed until B-lymphocyte surface antigen studies and a genetic analysis were conducted. We suggest that B-lymphocyte surface antigen studies and a BTK mutation analysis should be performed in familial patients with selective IgM deficiency to rule out atypical XLA.

  6. Hepatitis C and autoreactivity.

    Science.gov (United States)

    Bianchi, Francesco B; Muratori, Paolo; Granito, Alessandro; Pappas, Georgios; Ferri, Silvia; Muratori, Luigi

    2007-09-01

    After the discovery of HCV in 1989 a great amount of data has been produced in order to identify a possible aetiology for a number of idiopathic diseases, especially those with a suspected immune origin. Many associations have not been confirmed by prospective studies (as in the case of autoimmune hepatitis); other immune abnormalities, such as the emergence of non organ-specific autoantibodies and cryoglobulins, have been reported by many specific studies. To date, the link between HCV and autoreactivity is tentatively explained on the basis of sequence homologies shared by the HCV polyprotein and "self" proteins (such as CYP 2D6, target of anti-LKM1) (molecular mimicry mechanism); a second interpretation relies on the demonstration that the HCV - B lymphocyte interaction is able to induce a polyclonal B cell activation, an important cofactor for the development of clinically relevant B-lymphocyte autoimmune disorders. In this review we will focus on the major aspects of the autoimmune phenomena in HCV-infected patients, their clinical and therapeutical implications.

  7. Complement Receptor Type 1 Suppresses Human B Cell Functions in SLE Patients

    Directory of Open Access Journals (Sweden)

    Mariann Kremlitzka

    2016-01-01

    Full Text Available Complement receptors (CRs play an integral role in innate immunity and also function to initiate and shape the adaptive immune response. Our earlier results showed that complement receptor type 1 (CR1, CD35 is a potent inhibitor of the B cell receptor- (BCR- induced functions of human B lymphocytes. Here we show that this inhibition occurs already at the initial steps of B cell activation since ligation of CR1 reduces the BCR-induced phosphorylation of key signaling molecules such as Syk and mitogen activated protein kinases (MAPKs. Furthermore, our data give evidence that although B lymphocytes of active systemic lupus erythematosus (SLE patients express lower level of CR1, the inhibitory capacity of this complement receptor is still maintained and its ligand-induced clustering results in significant inhibition of the main B cell functions, similar to that found in the case of healthy individuals. Since we have found that reduced CR1 expression of SLE patients does not affect the inhibitory capacity of the receptor, our results further support the therapeutical potential of CD35 targeting the decrease of B cell activation and autoantibody production in autoimmune patients.

  8. Complement Receptor Type 1 Suppresses Human B Cell Functions in SLE Patients.

    Science.gov (United States)

    Kremlitzka, Mariann; Mácsik-Valent, Bernadett; Polgár, Anna; Kiss, Emese; Poór, Gyula; Erdei, Anna

    2016-01-01

    Complement receptors (CRs) play an integral role in innate immunity and also function to initiate and shape the adaptive immune response. Our earlier results showed that complement receptor type 1 (CR1, CD35) is a potent inhibitor of the B cell receptor- (BCR-) induced functions of human B lymphocytes. Here we show that this inhibition occurs already at the initial steps of B cell activation since ligation of CR1 reduces the BCR-induced phosphorylation of key signaling molecules such as Syk and mitogen activated protein kinases (MAPKs). Furthermore, our data give evidence that although B lymphocytes of active systemic lupus erythematosus (SLE) patients express lower level of CR1, the inhibitory capacity of this complement receptor is still maintained and its ligand-induced clustering results in significant inhibition of the main B cell functions, similar to that found in the case of healthy individuals. Since we have found that reduced CR1 expression of SLE patients does not affect the inhibitory capacity of the receptor, our results further support the therapeutical potential of CD35 targeting the decrease of B cell activation and autoantibody production in autoimmune patients.

  9. A prominent role for DC-SIGN+ dendritic cells in initiation and dissemination of measles virus infection in non-human primates.

    Directory of Open Access Journals (Sweden)

    Annelies W Mesman

    Full Text Available Measles virus (MV is a highly contagious virus that is transmitted by aerosols. During systemic infection, CD150(+ T and B lymphocytes in blood and lymphoid tissues are the main cells infected by pathogenic MV. However, it is unclear which cell types are the primary targets for MV in the lungs and how the virus reaches the lymphoid tissues. In vitro studies have shown that dendritic cell (DC C-type lectin DC-SIGN captures MV, leading to infection of DCs as well as transmission to lymphocytes. However, evidence of DC-SIGN-mediated transmission in vivo has not been established. Here we identified DC-SIGN(hi DCs as first target cells in vivo and demonstrate that macaque DC-SIGN functions as an attachment receptor for MV. Notably, DC-SIGN(hi cells from macaque broncho-alveolar lavage and lymph nodes transmit MV to B lymphocytes, providing in vivo support for an important role for DCs in both initiation and dissemination of MV infection.

  10. In vitro production of human anti-sperm antibodies: effect of an oligoclonal antibody (F6) on sperm-egg interaction.

    Science.gov (United States)

    Fusi, F M; Besuschio, F; De Santis, L; Lorenzetti, I; Ferrari, A

    1995-07-01

    A method has been developed to establish lines of transformed lymphocytes able to produce in vitro the same anti-sperm antibodies as those naturally occurring in immuno-infertile individuals. We utilized lymphocytes from a male donor whose serum contained anti-sperm antibodies of the IgG class up to the dilution 1:10,000, as detected by means of immunobead binding. T lymphocytes were separated from B lymphocytes using magnetic beads coated with anti-T antibody. B lymphocytes were then placed at a concentration of 5 x 10(6)/ml in a 96-well plate, stimulated with phytohaemagglutinin (PHA) and transformed with Epstein-Barr virus. After a few days, only transformed cells continued growing and these were collected. The supernatant was tested for production of anti-sperm antibodies and those transformed lymphocytes shown to be synthesising antibodies directed against the sperm head and the tail were cloned. We obtained a clone of cells producing antibodies of the IgG1 class directed against the head of the spermatozoon. This oligoclonal antibody (F6) recognized a 58-kDa band from a lysate of sperm membranes and was able to reduce the penetration of zona-free hamster oocytes by capacitated spermatozoa.

  11. Immunohistochemical study of porcine lung lesions associated with Pasteurella multocida.

    Science.gov (United States)

    Pors, Susanne E; Hansen, Mette S; Bisgaard, Magne; Jensen, Henrik E; Iburg, Tine M

    2013-08-01

    Infectious bronchopneumonia is a widespread disease in modern commercial pig production and Pasteurella multocida is frequently associated with the lesions. To evaluate porcine lung lesions associated with P. multocida, populations of inflammatory cells were examined by immunohistochemistry in necrotic lung lesions from nine pigs and exudative lung lesions from eleven pigs. Lungs from five pigs served as controls. All cases were selected from naturally infected pigs using co-infection based criteria to make them as comparable as possible. The inflammatory cells demonstrated by immunohistochemistry were T-lymphocytes (CD3(+), CD4(+) and CD8(+) subsets), B-lymphocytes, neutrophils, macrophages, and IgA(+), IgM(+) and IgG(+) cells. The results showed that (1) a significant increase in all inflammatory cells was found in lesions associated with P. multocida, (2) necrotic lesions had a larger number of CD3(+) T-lymphocytes and IgA(+) cells, and (3) cases with exudative lesions had a more CD8(+) T-lymphocytes, B-lymphocytes, macrophages and neutrophils. No differences in the numbers of CD4(+) T-lymphocytes, IgG(+) and IgM(+) positive cells were found between necrotic and exudative cases. The results show that P. multocida significantly alters the inflammatory response in the lung and that lesions associated with P. multocida display diverse inflammatory responses according to their distinct morphological pattern. Copyright © 2013 Elsevier Ltd. All rights reserved.

  12. Defective nonhomologous end joining blocks B-cell development in FLT3/ITD mice

    Science.gov (United States)

    Li, Li; Zhang, Li; Fan, Jinshui; Greenberg, Kathleen; Desiderio, Stephen; Rassool, Feyruz V.

    2011-01-01

    We have generated an FLT3/ITD knock-in mouse model in which mice with an FLT3/ITD mutation develop myeloproliferative disease (MPD) and a block in early B-lymphocyte development. To elucidate the role of FLT3/ITD signaling in B-cell development, we studied VDJ recombination in the pro-B cells of FLT3/ITD mice and discovered an increased frequency of DNA double strand breaks (DSBs) introduced by the VDJ recombinase. Early pro-B cells from FLT3/ITD mice were found to have a lower efficiency and decreased accuracy of DSB repair by nonhomologous end joining (NHEJ), which is required for rejoining DSBs during VDJ recombination. Reduced NHEJ repair probably results from reduced expression of Ku86, a key component of the classic DNA-PK-dependent NHEJ pathway. In compensation, early pro-B cells from FLT3/ITD cells mice show increased levels of the alternative, and highly error-prone, NHEJ pathway protein PARP1, explaining the increase in repair errors. These data suggest that, in early pro-B cells from FLT3/ITD mice, impairment of classic NHEJ decreases the ability of cells to complete postcleavage DSB ligation, resulting in failure to complete VDJ recombination and subsequent block of B-lymphocyte maturation. These findings might explain the poor prognosis of leukemia patients with constitutive activation of FLT3 signaling. PMID:21228325

  13. Aids-relaterede non-Hodgkin-lymfomer. Klinisk billede og prognose

    DEFF Research Database (Denmark)

    Penkowa, M; Hansen, P B

    1998-01-01

    Patients infected with HIV are at high risk for developing non-Hodgkin's lymphomas (NHL). HIV-associated NHLs seem to be increasing in number. They consist of two major histopathological subtypes originating from B-lymphocytes: Burkitt-like lymphomas and diffuse large cell lymphomas. There seems ...... below 130 x 10(9)/l, widespread symptoms of disease, presence of EBV in the lymphoma and immunoblastic histology. Udgivelsesdato: 1998-Apr-27......Patients infected with HIV are at high risk for developing non-Hodgkin's lymphomas (NHL). HIV-associated NHLs seem to be increasing in number. They consist of two major histopathological subtypes originating from B-lymphocytes: Burkitt-like lymphomas and diffuse large cell lymphomas. There seems...... to be a clear association between Epstein-Barr virus (EBV) and immunoblastic lymphomas (a subtype of large cell lymphomas) in AIDS patients. Patients with AIDS often have widespread disease at presentation and frequent involvement of extranodal sites (CNS, liver, bone marrow, the digestive tract and skin...

  14. Transmembrane signaling through major histocompatibility complex (MHC) encoded molecules

    International Nuclear Information System (INIS)

    Newell, M.K.

    1987-01-01

    The importance of the major histocompatibility complex (MHC) encoded molecules has traditionally been ascribed to the role these molecules play as restriction elements for T lymphocytes. This is, in order for T cell activation to occur the T cell must recognize antigen in association with MHC molecules. More controversial, however, is the potential role MHC molecules play as signal transducing receptors/acceptors to the B lymphocyte. In other words, do class II MHC molecules (Ia antigens) actively transduce a signal to the B cell which drives its differentiation into an antibody secreting cell? Two approaches to this question are described. The first involves biochemical characterization of those molecules which consistently copurify with I-A/sup k/ by two dimensional gel electrophoresis. The second approach utilizes two types of analyses: first, an examination of the biochemical changes which occur in the cell as a result of Ia ligation; and second, analysis of changes in the B cell's physiological response as a result of Ia perturbation. Molecules were examined which may couple the antigen binding event in the B lymphocyte to the antigen driven signal transduction cascade which ultimately leads to immunoglobulin secretion. In these experiments, cells were labelled with [ 32 P] and stimulated cells with phorbol myristate acetate. The membrane form of immunoglobulin was then isolated from detergent lysates of whole cells and passed over an anti-k affinity column. The eluates were analyzed by SDS-PAGE

  15. Influence of molecular weight on in vitro immunostimulatory properties of instant coffee.

    Science.gov (United States)

    Passos, Cláudia P; Cepeda, Márcio R; Ferreira, Sónia S; Nunes, Fernando M; Evtuguin, Dmitry V; Madureira, Pedro; Vilanova, Manuel; Coimbra, Manuel A

    2014-10-15

    Instant coffee was prepared and fractionated into higher (>100kDa), medium (5-10, 10-30, 30-100kDa) and lower (1-5, composition characteristics of arabinogalactans and galactomannans were recovered in all fractions. Also, amino acid analysis performed after hydrolysis showed similar compositions in all fractions. On the contrary, free chlorogenic acids and caffeine were only detected in the lowest molecular weight fraction (<1kDa). A direct relationship between the melanoidins browning index and the molecular weight was observed. The fractions obtained were incubated in vitro with murine spleen lymphocytes in order to evaluate their possible immunostimulatory abilities. The surface expression of CD69 (early activation marker) on different lymphocyte sub-populations showed that the fraction with 1-5kDa was able to induce activation of B-lymphocytes. This was the only fraction to induce B-lymphocyte activation, since all the other fractions failed, even when higher concentrations were used. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. Most B cells in non-lymphoid tissues are naïve.

    Science.gov (United States)

    Inman, Charlotte F; Murray, Tamsin Zangerle; Bailey, Mick; Cose, Stephen

    2012-02-01

    The current view of lymphocyte migration states that naïve lymphocytes re-circulate between the blood and the lymph via the lymph nodes, but are not able to access non-lymphoid tissues. We examined B lymphocytes in peripheral tissues and found that the majority were phenotypically similar to naïve B cells in lymphoid tissues and were located within the parenchyma, not associated with blood vessels. The mutation rate within the Vh region of these cells was substantially less than the rate attributed to somatic hypermutation and was identical to that observed in naïve B cells isolated from the lymph nodes, showing the presence of naïve B cells in the non-lymphoid organs. Further, using FTY720-treated mice, we showed that naïve B cells migrate through the peripheral tissues and, using pertussis toxin, that the entry of B cells was not controlled by chemokine-mediated signalling events. Overall, these results show that naïve B lymphocytes constitute the majority of the total B-cell population in non-lymphoid tissues and suggest that these cells may re-circulate through the periphery as part of their normal migration pathway. This has implications for the current view of the role of naïve B cells in priming and tolerance.

  17. Circulating immune cells in multiple sclerosis.

    Science.gov (United States)

    Jones, A P; Kermode, A G; Lucas, R M; Carroll, W M; Nolan, D; Hart, P H

    2017-02-01

    Circulating T and B lymphocytes contribute to the pathogenesis of the neuroinflammatory autoimmune disease, multiple sclerosis (MS). Further progress in the development of MS treatments is dependent upon a greater understanding of the immunological disturbances that underlie the disease. Analyses of circulating immune cells by flow cytometry have revealed MS-associated alterations in the composition and function of T and B cell subsets, including temporal changes associated with disease activity. Disturbances in circulating immune populations reflect those observed in the central nervous system and include skewing towards proinflammatory CD4 + and CD8 + T cells and B cells, greater proportions of follicular T helper cells and functional defects in the corresponding T and B regulatory subsets. Utilizing the analytical power of modern flow cytometers, researchers are now well positioned to monitor immunological changes associated with disease activity or intervention, describe immunological signatures with predictive value and identify targets for therapeutic drug development. This review discusses the contribution of various T and B lymphocyte subsets to MS pathogenesis, provides current and relevant phenotypical descriptions to assist in experimental design and highlights areas of future research. © 2016 British Society for Immunology.

  18. Lymphocyte subset reference intervals in blood donors from northeastern Brazil

    Directory of Open Access Journals (Sweden)

    ALEX J.L. TORRES

    2015-06-01

    Full Text Available The reference intervals for leukocytes and lymphocytes currently used by most clinical laboratories present limitations as they are primarily derived from individuals of North American and European origin. The objective this study was to determine reference values for peripheral blood B lymphocytes, T lymphocyte subsets (CD4+, CD8+, naïve, memory, regulatory, TCRαβ and TCRγδ+ and NK cells from blood donors in Salvador-Bahia, Brazil. Results: The proportion of included male subjects was 73.7% and the median ages of males (34 and females (35 were found to be similar. Absolute counts total lymphocytes subsets to both gender was 1,956 (1,060-4,186 cells and relative values 34%. The T CD4+ and T CD8+ lymphocytes relative values was 51% (20-62 and 24% (9-28, respectively. The most statistically significant finding observed was a higher percentage of B lymphocytes (p=0.03 in females. Commonly cited subset reference intervals were found to be consistent with values in several populations from different geographic areas.

  19. Naegleria fowleri immunization modifies lymphocytes and APC of nasal mucosa.

    Science.gov (United States)

    Carrasco-Yepez, M M; Campos-Rodríguez, R; Reséndiz-Albor, A A; Peña-Juárez, C; Contis-Montes de Oca, A; Arciniega-Martínez, I M; Bonilla-Lemus, P; Rojas-Hernandez, S

    2018-03-01

    We investigated whether intranasal immunization with amoebic lysates plus cholera toxin modified the populations of T and B lymphocytes, macrophages and dendritic cells by flow cytometry from nose-associated lymphoid tissue (NALT), cervical lymph nodes (CN), nasal passages (NP) and spleen (SP). In all immunized groups, the percentage of CD4 was higher than CD8 cells. CD45 was increased in B cells from mice immunized. We observed IgA antibody-forming cell (IgA-AFC) response, mainly in NALT and NP. Macrophages from NP and CN expressed the highest levels of CD80 and CD86 in N. fowleri lysates with either CT or CT alone immunized mice, whereas dendritic cells expressed high levels of CD80 and CD86 in all compartment from immunized mice. These were lower than those expressed by macrophages. Only in SP from CT-immunized mice, these costimulatory molecules were increased. These results suggest that N. fowleri and CT antigens are taking by APCs, and therefore, protective immunity depends on interactions between APCs and T cells from NP and CN. Consequently, CD4 cells stimulate the differentiation from B lymphocytes to AFC IgA-positive; antibody that we previously found interacting with trophozoites in the nasal lumen avoiding the N. fowleri attachment to nasal epithelium. © 2017 John Wiley & Sons Ltd.

  20. Aeromonas salmonicida Infection Only Moderately Regulates Expression of Factors Contributing to Toll-Like Receptor Signaling but Massively Activates the Cellular and Humoral Branches of Innate Immunity in Rainbow Trout (Oncorhynchus mykiss

    Directory of Open Access Journals (Sweden)

    Andreas Brietzke

    2015-01-01

    Full Text Available Toll-like receptors (TLRs are known to detect a defined spectrum of microbial structures. However, the knowledge about the specificity of teleost Tlr factors for distinct pathogens is limited so far. We measured baseline expression profiles of 18 tlr genes and associated signaling factors in four immune-relevant tissues of rainbow trout Oncorhynchus mykiss. Intraperitoneal injection of a lethal dose of Aeromonas salmonicida subsp. salmonicida induced highly increased levels of cytokine mRNAs during a 72-hour postinfection (hpi period. In contrast, only the fish-specific tlr22a2 and the downstream factor irak1 featured clearly increased transcript levels, while the mRNA concentrations of many other tlr genes decreased. Flow cytometry quantified cell trafficking after infection indicating a dramatic influx of myeloid cells into the peritoneum and a belated low level immigration of lymphoid cells. T and B lymphocytes were differentiated with RT-qPCR revealing that B lymphocytes emigrated from and T lymphocytes immigrated into head kidney. In conclusion, no specific TLR can be singled out as a dominant receptor for A. salmonicida. The recruitment of cellular factors of innate immunity rather than induced expression of pathogen receptors is hence of key importance for mounting a first immune defense against invading A. salmonicida.

  1. Modification of immunopharmacological activities of synthetic monosaccharide lipid A analogue, GLA60, by lysozyme.

    Science.gov (United States)

    Tanida, N; Ohno, N; Adachi, Y; Matsuura, M; Nakano, M; Kiso, M; Hasegawa, A; Yadomae, T

    1992-11-01

    Recent studies by our group suggested that lysozyme has a high affinity for bacterial lipopolysaccharide (LPS) of both the smooth and rough forms, and inhibits various immunomodulatory activities of LPS. GLA60 is a synthetic monosaccharide analogue of bacterial lipid A well known as having most of the activities of lipid A with very low toxicity. In this study, we characterized the interaction of lysozyme with GLA60 in comparison to that with Escherichia coli 0111 LPS (smooth form) by means of an immunopharmacological approach. Using dansylated lysozyme (DNS-LZM) as a probe, LZM was found to bind to GLA60. The mitogenic and polyclonal B-cell activating activities were significantly reduced by complex formation. However, there was no inhibitory effect on GLA60 induced production of IL-1 and TNF of macrophages. Interestingly, the activities of macrophages induced by the complex were found to be significantly higher than those induced by GLA60 itself. In contrast, the activities of 0111 LPS were significantly inhibited by LZM. Since the GLA60-LZM complex produced a turbid suspension but the 0111 LPS-LZM complex remained soluble, we consider that the activities of GLA60 alone were mediated by the common functional LPS receptor for dispersed form in both macrophages and B-lymphocytes, but activation of macrophages by the complex was mediated either by another LPS receptor not present in B-lymphocytes or through the phagocytic function of macrophages.

  2. A comparison between protein profiles of B cell subpopulations and mantle cell lymphoma cells

    Directory of Open Access Journals (Sweden)

    Lehtiö Janne

    2009-11-01

    Full Text Available Abstract Background B-cell lymphomas are thought to reflect different stages of B-cell maturation. Based on cytogenetics and molecular markers, mantle cell lymphoma (MCL is presumed to derive predominantly from naïve, pre-germinal centre (pre-GC B lymphocytes. The aim of this study was to develop a method to investigate the similarity between MCL cells and different B-cell compartments on a protein expression level. Methods Subpopulations of B cells representing the germinal centre (GC, the pre-GC mantle zone and the post-GC marginal zone were isolated from tonsils using automated magnetic cell sorting (AutoMACS of cells based on their expression of CD27 and IgD. Protein profiling of the B cell subsets, of cell lines representing different lymphomas and of primary MCL samples was performed using top-down proteomics profiling by surface-enhanced laser detection/ionization time-of-flight mass spectrometry (SELDI-TOF-MS. Results Quantitative MS data of significant protein peaks (p-value Conclusion AutoMACS sorting generates sufficient purity to enable a comparison between protein profiles of B cell subpopulations and malignant B lymphocytes applying SELDI-TOF-MS. Further validation with an increased number of patient samples and identification of differentially expressed proteins would enable a search for possible treatment targets that are expressed during the early development of MCL.

  3. Identification of a novel dendritic cell surface antigen defined by carbohydrate specific CD24 antibody cross-reactivity.

    Science.gov (United States)

    Williams, L A; McLellan, A D; Summers, K L; Sorg, R V; Fearnley, D B; Hart, D N

    1996-01-01

    Dendritic cells (DC) are characterized as leucocytes that lack mature lineage specific markers and stimulate naive T-lymphocyte proliferation in vitro and in vivo. The mouse heat stable antigen (HSA) participates in T lymphocyte co-stimulation and is expressed by DC isolated from thymus, skin and spleen. The human HSA homologue, CD24, is predominantly expressed by B lymphocytes and granulocytes, but its expression on DC has not been studied in detail. CD24 clearly participates in B-lymphocyte signalling but co-stimulatory activity for T lymphocytes has not yet been described. We have examined the expression of CD24 on human peripheral blood DC populations isolated directly or following in vitro culture. The CD24 antigen was absent from blood DC however, cross-reactive sialylated carbohydrate epitopes were detected on DC with some CD24 monoclonal antibodies (mAb). These CD24 mAb define a protein surface antigen, which is expressed by an immature or resting subpopulation of peripheral blood DC and is down-regulated following activation differentiation in vitro. PMID:8911149

  4. Expression profiles of prion and doppel proteins and of their receptors in mouse splenocytes.

    Science.gov (United States)

    Cordier-Dirikoc, Sevda; Zsürger, Nicole; Cazareth, Julie; Ménard, Baptiste; Chabry, Joëlle

    2008-08-01

    Doppel (Dpl) shares common structural features with the prion protein (PrP) whose pathologic isoform is considered as the causative agent of prion diseases. Although their physiological functions in the immune system remain largely unknown, we demonstrated that substantial amounts of PrP and Dpl are expressed by spleen cells notably B lymphocytes, granulocytes and DC, but not T lymphocytes and NK. To characterize trans-interacting partners of PrP and Dpl on mouse splenocytes, fluorescent PrP and Dpl tetramers were produced and used as tracers. Both tetramers specifically bind to B lymphocytes, dendritic cells, macrophages and granulocytes and in a lesser extend to T lymphocytes. No binding was observed on NK, follicular dendritic cells and mesenchymal spleen cells. The activation of intracellular transduction signals (i.e. intracellular calcium concentration and activation of the MAP kinase pathway) suggested that PrP and Dpl tetramers bind to functional receptors on B cells. None of the previously described PrP partners account for the binding sites characterized here. Our study suggests a possible role for PrP and Dpl in the cell-cell interactions in the immune system.

  5. Alterations in TP53, cyclin D2, c-Myc, p21WAF1/CIP1 and p27KIP1 expression associated with progression in B-CLL

    Directory of Open Access Journals (Sweden)

    Antosz Halina

    2010-04-01

    Full Text Available B-cell chronic lymphocytic leukaemia (B-CLL originates from B lymphocytes that may differ in the activationlevel, maturation state or cellular subgroups in peripheral blood. Tumour progression in CLL B cells seems to result in gradualaccumulation of the clone of resting B lymphocytes in the early phases (G0/G1 of the cell cycle. The G1 phase isimpaired in B-CLL. We investigated the gene expression of five key cell cycle regulators: TP 53, c-Myc, cyclin D2,p21WAF1/CIP1 and p27KIP1, which primarily regulate the G1 phase of the cell cycle, or S-phase entry and ultimately controlthe proliferation and cell growth as well as their role in B-CLL progression. The study was conducted in peripheral bloodCLL lymphocytes of 40 previously untreated patients. Statistical analysis of correlations of TP53, cyclin D2, c-Myc,p21WAF1/CIP1 and p27KIP1 expressions in B-CLL patients with different Rai stages demonstrated that the progression of diseasewas accompanied by increases in p53, cyclin D2 and c-Myc mRNA expression. The expression of p27KIP1 was nearlystatistically significant whereas that of p21 WAF1/CIP1 showed no such correlation. Moreover, high expression levels of TP53and c-Myc genes were found to be closely associated with more aggressive forms of the disease requiring earlier therapy.

  6. Immunophenotypic lymphocyte profiles in human african trypanosomiasis.

    Directory of Open Access Journals (Sweden)

    Caroline Boda

    Full Text Available Human African trypanosomiasis (HAT is a deadly vector-born disease caused by an extracellular parasite, the trypanosome. Little is known about the cellular immune responses elicited by this parasite in humans. We used multiparameter flow cytometry to characterize leukocyte immunophenotypes in the blood and cerebrospinal fluid (CSF of 33 HAT patients and 27 healthy controls identified during a screening campaign in Angola and Gabon. We evaluated the subsets and activation markers of B and T lymphocytes. Patients had a higher percentage of CD19+ B lymphocytes and activated B lymphocytes in the blood than did controls, but lacked activated CD4+ T lymphocytes (CD25+. Patients displayed no increase in the percentage of activated CD8+ T cells (HLA-DR+, CD69+ or CD25+, but memory CD8 T-cell levels (CD8+CD45RA2 were significantly lower in patients than in controls, as were effector CD8 T-cell levels (CD8+CD45RA+CD62L2. No relationship was found between these blood immunophenotypes and disease severity (stage 1 vs 2. However, CD19+ B-cell levels in the CSF increased with disease severity. The patterns of T and B cell activation in HAT patients suggest that immunomodulatory mechanisms may operate during infection. Determinations of CD19+ B-cell levels in the CSF could improve disease staging.

  7. Some Immunophysiological Features of Sport Activity in the Climatic and Geographical Conditions of the Middle Ob Region.

    Science.gov (United States)

    Kuchin, R V; Nenenko, N D; Chernitsyna, N V

    2017-01-01

    We analyzed the cellular and humoral.components of immune system in athletes who were born, lived and trained in the conditions of the Middle Ob Region (Khanty-Mansi Autonomous Okrug - Ugra). The main group included young males and females engaged in cross country skiing (12 males, 10 females) and volleyball (11 males, 10 females). The control group (normal inhabitants of the region) consisted of 10 males and 10 females who were born and currently live in. KMAO-Ugra and do not do any sports on a regular basis. The age of subjects ranged from 19 to 22 years. It was found that the indices of cell and humoral components of immune system differed slightly between young women in the control and main groups. As for men, a significant decrease in total leukocyte, neutrophil and lymphocyte counts were observed; a decrease in the parameters of humoral immunity (b-lymphocytes and IgA) was also observed in male skiers. It was found that the total leukocyte count, the level of B-lymphocytes and the concentration of IgG in men who live in the Middle Ob region and do not do any sports is higher than in women of the same group.

  8. A Typical Immune T/B Subset Profile Characterizes Bicuspid Aortic Valve: In an Old Status?

    Directory of Open Access Journals (Sweden)

    Carmela R. Balistreri

    2018-01-01

    Full Text Available Bicuspid valve disease is associated with the development of thoracic aortic aneurysm. The molecular mechanisms underlying this association still need to be clarified. Here, we evaluated the circulating levels of T and B lymphocyte subsets associated with the development of vascular diseases in patients with bicuspid aortic valve or tricuspid aortic valve with and without thoracic aortic aneurysm. We unveiled that the circulating levels of the MAIT, CD4+IL−17A+, and NKT T cell subsets were significantly reduced in bicuspid valve disease cases, when compared to tricuspid aortic valve cases in either the presence or the absence of thoracic aortic aneurysm. Among patients with tricuspid aortic valve, these cells were higher in those also affected by thoracic aortic aneurysm. Similar data were obtained by examining CD19+ B cells, naïve B cells (IgD+CD27−, memory unswitched B cells (IgD+CD27+, memory switched B cells (IgD−CD27+, and double-negative B cells (DN (IgD−CD27−. These cells resulted to be lower in subjects with bicuspid valve disease with respect to patients with tricuspid aortic valve. In whole, our data indicate that patients with bicuspid valve disease show a quantitative reduction of T and B lymphocyte cell subsets. Future studies are encouraged to understand the molecular mechanisms underlying this observation and its pathophysiological significance.

  9. Hibernation is associated with depression of T-cell independent humoral immune responses in the 13-lined ground squirrel.

    Science.gov (United States)

    Bouma, Hjalmar R; Henning, Robert H; Kroese, Frans G M; Carey, Hannah V

    2013-03-01

    Mammalian hibernation consists of periods of low metabolism and body temperature (torpor), interspersed by euthermic arousal periods. The function of both the innate and adaptive immune system is suppressed during hibernation. In this study, we analyzed the humoral adaptive immune response to a T-cell independent (TI-2) and a T-cell dependent (TD) antigen. Thirteen-lined ground squirrels were immunized in summer or during hibernation with either a TI-2 or TD antigen on day 0 and day 14. Blood was drawn on day 0, 7, 14, 21 and 28. Both types of antigens induced a significant rise in antibody titer in summer animals. Much to our surprise, however, only immunization with the TD antigen, and not with the TI-2 antigen induced a humoral response in hibernators. Flow cytometric analysis of CD4 (helper T-lymphocytes), CD8 (cytotoxic T-lymphocytes) and CD45RA (B-lymphocytes) in blood, spleen and lymph nodes ruled out massive apoptosis as explanation of the absent TI humoral response during hibernation. Rather, reduced TI-2 stimulation of B-lymphocytes, possibly due to lowered serum complement during torpor, may explain the reduced antibody production in response to a TI-2 antigen. These results demonstrate that hibernation diminishes the capacity to induce a TI-2 humoral immune response, while the capacity to induce a humoral response to a TD antigen is maintained. Copyright © 2012 Elsevier Ltd. All rights reserved.

  10. Alteration of Lymphocyte Phenotype and Function in Sickle Cell Anemia: Implications for Vaccine Responses

    Science.gov (United States)

    Balandya, Emmanuel; Reynolds, Teri; Obaro, Stephen; Makani, Julie

    2016-01-01

    Individuals with sickle cell anemia (SCA) have increased susceptibility to infections, secondary to impairment of immune function. Besides the described dysfunction in innate immunity, including impaired opsonization and phagocytosis of bacteria, evidence of dysfunction of T and B lymphocytes in SCA has also been reported. This includes reduction in the proportion of circulating CD4+ and CD8+ T cells, reduction of CD4+ helper : CD8+ suppressor T cell ratio, aberrant activation and dysfunction of regulatory T cells (Treg), skewing of CD4+ T cells towards Th2 response and loss of IgM-secreting CD27+IgMhighIgDlow memory B cells. These changes occur on the background of immune activation characterized by predominance of memory CD4+ T cell phenotypes, increased Th17 signaling and elevated levels of C-reactive protein and pro-inflammatory cytokines IL-6 and TNF-α, which may affect the immunogenicity and protective efficacy of vaccines available to prevent infections in SCA. Thus, in order to optimize the use of vaccines in SCA, a thorough understanding of T and B lymphocyte functions and vaccine reactivity among individuals with SCA is needed. Studies should be encouraged of different SCA populations, including sub-Saharan Africa where the burden of SCA is highest. This article summarizes our current understanding of lymphocyte biology in SCA, and highlights areas that warrant future research. PMID:27237467

  11. Effect of radiotherapy and splenectomy on the bone marrow status in patients with Hodgkin's disease

    International Nuclear Information System (INIS)

    Bajsogolov, G.D.; Pavlov, V.V.; Bogatyreva, T.I.; Khait, S.E.; Kuz'mina, E.G.; Khoptynskaya, S.K.; Kolesnikova, A.I.

    1987-01-01

    A study was made of the bone marrow status in unirradiated zones on 33 patients with stage 1-2 Hodgkin's disease in complete 9-12 year remission after therapeutic irradiation of the lymphatic collectors of the upper part of the trunk in combination with irradiation of the system (16 patients) or splenectomy (17 patients). The total count of myelokaryocytes, myelogram, a relative and absolute content of lymphoid cells, immature granulocytes and elements of the erythroid series were defined in the punctates of the upper portion of the ilium. T- and B-lymphocyte count, the number of granulocytomacrophage (CFU-C) and stromal (CFU-F) precursor cells were defined using morphocytochemical and immunological methods. At that time an increase in the relative and absolute content of C- ad B-lymphocytes was noted. The T-cell count and the total number of myelokaryocytes, on the one hand, and the content of immature granulocytes and erythronormoblasts, on the other had, showed correlation of various degree which was particularly noticeable in the group of unoperated patients. The total number of myelokaryocytes in 1 μl of the bone marrow of the patients after splenectomy, on an average, significantly exceeded that in the group of patients with the irradiated spleen. These changes were considered to be a result of the rearragement of T-differentiating lymphocytes with their raised accumulation in the bone marrow after irradiation of a considerable volume of the lymphoid tissue and spleen or after splenectomy

  12. Vitamin D endocrine system involvement in autoimmune rheumatic diseases.

    Science.gov (United States)

    Cutolo, Maurizio; Pizzorni, Carmen; Sulli, Alberto

    2011-12-01

    Vitamin D is synthesized from cholesterol in the skin (80-90%) under the sunlight and then metabolized into an active D hormone in liver, kidney and peripheral immune/inflammatory cells. These endocrine-immune effects include also the coordinated activities of the vitamin D-activating enzyme, 1alpha-hydroxylase (CYP27B1), and the vitamin D receptor (VDR) on cells of the immune system in mediating intracrine and paracrine actions. Vitamin D is implicated in prevention and protection from chronic infections (i.e. tubercolosis), cancer (i.e. breast cancer) and autoimmune rheumatic diseases since regulates both innate and adaptive immunity potentiating the innate response (monocytes/macrophages with antimicrobial activity and antigen presentation), but suppressing the adaptive immunity (T and B lymphocyte functions). Vitamin D has modulatory effects on B lymphocytes and Ig production and recent reports have demonstrated that 1,25(OH)2D3 does indeed exert direct effects on B cell homeostasis. A circannual rhythm of trough vitamin D levels in winter and peaks in summer time showed negative correlation with clinical status at least in rheumatoid arthritis and systemic lupus erythematosus. Recently, the onset of symptoms of early arthritis during winter or spring have been associated with greater radiographic evidence of disease progression at 12 months possibly are also related to seasonal lower vitamin D serum levels. Copyright © 2011 Elsevier B.V. All rights reserved.

  13. Developmental exposure to diuron causes splenotoxicity in male Sprague-Dawley rat pups.

    Science.gov (United States)

    Domingues, Alexandre; Grassi, Tony F; Spinardi-Barbisan, Ana L T; Barbisan, Luís F

    2012-01-01

    This study investigated whether perinatal exposure to diuron [3-(3,4-dichlorophenyl)-1-1-dimethylurea] might exert adverse effects on rat lymphoid organs. Pregnant Sprague-Dawley (SD) rats were exposed to diuron at 500, 750 or 1250 ppm in the diet from gestational days (GD) 12-21 and during lactation. At postnatal day (PND) 42, male pups were euthanized and thymus, spleen, mesenteric lymph node and femur were collected for histopathological analysis. Food consumption and body weight gain were significantly reduced in dams exposed to 1250 ppm during gestation period. Also, Diuron at 750 and 1250 ppm produced: (1) increased relative spleen weight associated histologically with severe congestion in red pulp, (2) enhanced extramedullary hematopoiesis and hemosiderosis as well as (3) depletion of lymphoid follicles in white pulp. Flow cytometric analysis revealed a significant reduction in B lymphocytes (CD45RA+) in male pups but T lymphocytes (CD4+, CD8+ and CD4+/CD8+) were not markedly affected. Thus, data suggest that Diuron-induced maternal toxicity in dams exposed to high dose and perinatal exposure to this herbicide produced spleen toxicity as evidenced by a reduction in B lymphocyte number in male SD pups.

  14. MHC class I-associated peptides derive from selective regions of the human genome.

    Science.gov (United States)

    Pearson, Hillary; Daouda, Tariq; Granados, Diana Paola; Durette, Chantal; Bonneil, Eric; Courcelles, Mathieu; Rodenbrock, Anja; Laverdure, Jean-Philippe; Côté, Caroline; Mader, Sylvie; Lemieux, Sébastien; Thibault, Pierre; Perreault, Claude

    2016-12-01

    MHC class I-associated peptides (MAPs) define the immune self for CD8+ T lymphocytes and are key targets of cancer immunosurveillance. Here, the goals of our work were to determine whether the entire set of protein-coding genes could generate MAPs and whether specific features influence the ability of discrete genes to generate MAPs. Using proteogenomics, we have identified 25,270 MAPs isolated from the B lymphocytes of 18 individuals who collectively expressed 27 high-frequency HLA-A,B allotypes. The entire MAP repertoire presented by these 27 allotypes covered only 10% of the exomic sequences expressed in B lymphocytes. Indeed, 41% of expressed protein-coding genes generated no MAPs, while 59% of genes generated up to 64 MAPs, often derived from adjacent regions and presented by different allotypes. We next identified several features of transcripts and proteins associated with efficient MAP production. From these data, we built a logistic regression model that predicts with good accuracy whether a gene generates MAPs. Our results show preferential selection of MAPs from a limited repertoire of proteins with distinctive features. The notion that the MHC class I immunopeptidome presents only a small fraction of the protein-coding genome for monitoring by the immune system has profound implications in autoimmunity and cancer immunology.

  15. B cells and ectopic follicular structures: novel players in anti-tumor programming with prognostic power for patients with metastatic colorectal cancer.

    Directory of Open Access Journals (Sweden)

    Anastasia Meshcheryakova

    Full Text Available Remarkably limited information is available about biological mechanisms that determine the disease entity of metastatic colorectal cancer in the liver (CRCLM with no good clinical parameters to estimate prognosis. For the last few years, understanding the relationship between tumor characteristics and local immune response has gained increasing attention. Given the multifaceted roles of B-cell-driven responses, we aimed to elucidate the immunological imprint of B lymphocytes at the metastatic site, the interrelation with macrophages, and their prognostic relevance. Here we present novel algorithm allowing to assess a link between the local patient-specific immunological capacity and clinical outcome. The microscopy-based imaging platform was used for automated scanning of large-scale tissue sections and subsequent qualitative and quantitative analyses of immune cell subtypes using lineage markers and single-cell recognition strategy. Results indicate massive infiltration of CD45-positive leukocytes confined to the metastatic border. We report for the first time the accumulation of CD20-positive B lymphocytes at the tumor-liver interface comprising the major population within the large CD45-positive aggregates. Strikingly, functionally active, activation-induced cytidine deaminase (AID-positive ectopic lymphoid structures were found to be assembled within the metastatic margin. Furthermore, the CD20-based data set revealed a strong prognostic power: patients with high CD20 content and/or ectopic follicles had significantly lower risk for disease recurrence as revealed by univariate analysis (p<0.001 for both and in models adjusted for clinicopathological variables (p<0.001 and p = 0.01, respectively, and showed prolonged overall survival. In contrast, CD68 staining-derived data set did not show an association with clinical outcome. Taken together, we nominate the magnitude of B lymphocytes, including those organized in ectopic follicles, as

  16. Altered Distribution of Peripheral Blood Maturation-Associated B-Cell Subsets in Chronic Alcoholism.

    Science.gov (United States)

    Almeida, Julia; Polvorosa, Maria Angeles; Gonzalez-Quintela, Arturo; Madruga, Ignacio; Marcos, Miguel; Pérez-Nieto, Maria Angeles; Hernandez-Cerceño, Maria Luisa; Orfao, Alberto; Laso, Francisco Javier

    2015-08-01

    Although decreased counts of peripheral blood (PB) B cells-associated with an apparently contradictory polyclonal hypergammaglobulinemia-have been reported in chronic alcoholism, no information exists about the specific subsets of circulating B cells altered and their relationship with antibody production. Here, we analyzed for the first time the distribution of multiple maturation-associated subpopulations of PB B cells in alcoholism and its potential relationship with the onset of liver disease. PB samples from 35 male patients-20 had alcoholic hepatitis (AH) and 15 chronic alcoholism without liver disease (AWLD)-were studied, in parallel to 19 male healthy donors (controls). The distribution of PB B-cell subsets (immature/regulatory, naïve, CD27(-) and CD27(+) memory B lymphocytes, and circulating plasmablasts of distinct immunoglobulin-Ig-isotypes) was analyzed by flow cytometry. Patients with AH showed significantly decreased numbers of total PB B lymphocytes (vs. controls and AWLD), at the expense of immature, memory, and, to a lesser extent, also naïve B cells. AWLD showed reduced numbers of immature and naïve B cells (vs. controls), but higher PB counts of plasmablasts (vs. the other 2 groups). Although PB memory B cells were reduced among the patients, the percentage of surface (s)IgA(+) cells (particularly CD27(-) /sIgA(+) cells) was increased in AH, whereas both sIgG(+) and sIgA(+) memory B cells were significantly overrepresented in AWLD versus healthy donors. Regarding circulating plasmablasts, patients with AH only showed significantly reduced counts of sIgG(+) cells versus controls. In contrast, the proportion of both sIgA(+) and sIgG(+) plasmablasts-from all plasmablasts-was reduced in AH and increased in AWLD (vs. the other 2 groups). AH and AWLD patients display a significantly reduced PB B-cell count, at the expense of decreased numbers of recently produced immature/regulatory B cells and naïve B cells, together with an increase in Ig

  17. Effect of roflumilast on inflammatory cells in the lungs of cigarette smoke-exposed mice

    Directory of Open Access Journals (Sweden)

    De Cunto Giovanna

    2008-08-01

    Full Text Available Abstract Background We reported that roflumilast, a phosphodiesterase 4 inhibitor, given orally at 5 mg/kg to mice prevented the development of emphysema in a chronic model of cigarette smoke exposure, while at 1 mg/kg was ineffective. Here we investigated the effects of roflumilast on the volume density (VV of the inflammatory cells present in the lungs after chronic cigarette smoke exposure. Methods Slides were obtained from blocks of the previous study and VV was assessed immunohistochemically and by point counting using a grid with 48 points, a 20× objective and a computer screen for a final magnification of 580×. Neutrophils were marked with myeloperoxidase antibody, macrophages with Mac-3, dendritic cells with fascin, B-lymphocytes with B220, CD4+ T-cells with CD4+ antibody, and CD8+T-cells with CD8-α. The significance of the differences was calculated using one-way analysis of variance. Results Chronic smoke exposure increased neutrophil VV by 97%, macrophage by 107%, dendritic cell by 217%, B-lymphocyte by 436%, CD4+ by 524%, and CD8+ by 417%. The higher dose of roflumilast prevented the increase in neutrophil VV by 78%, macrophage by 82%, dendritic cell by 48%, B-lymphocyte by 100%, CD4+ by 98% and CD8+ VV by 88%. The lower dose of roflumilast did not prevent the increase in neutrophil, macrophage and B-cell VV but prevented dendritic cells by 42%, CD4+ by 55%, and CD8+ by 91%. Conclusion These results indicate (i chronic exposure to cigarette smoke in mice results in a significant recruitment into the lung of inflammatory cells of both the innate and adaptive immune system; (ii roflumilast at the higher dose exerts a protective effect against the recruitment of all these cells and at the lower dose against the recruitment of dendritic cells and T-lymphocytes; (iii these findings underline the role of innate immunity in the development of pulmonary emphysema and (iiii support previous results indicating that the inflammatory cells of

  18. Spinal cord injury, immunodepression, and antigenic challenge.

    Science.gov (United States)

    Held, Katherine S; Lane, Thomas E

    2014-10-01

    The inability to effectively control microbial infection is a leading cause of morbidity and mortality in individuals affected by spinal cord injury (SCI). Available evidence from clinical studies as well as animal models of SCI demonstrate that increased susceptibility to infection is derived from disruption of central nervous system (CNS) communication with the host immune system that ultimately leads to immunodepression. Understanding the molecular and cellular mechanisms governing muted cellular and humoral responses that occur post-injury resulting in impaired host defense following infection is critical for improving the overall quality of life of individuals with SCI. This review focuses on studies performed using preclinical animal models of SCI to evaluate how injury impacts T and B lymphocyte responses following either viral infection or antigenic challenge. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Mechanisms of protective immunity against Schistosoma mansoni infection in mice vaccinated with irradiated cercariae. V. Anamnestic cellular and humoral responses following challenge infection

    International Nuclear Information System (INIS)

    Correa-Oliveira, R.; Sher, A.; James, S.L.

    1984-01-01

    Mice vaccinated with radiation-attenuated cercariae display low levels of cellular and humoral immune responses toward schistosomulum antigens, as measured in vitro by lymphocyte blastogenesis and quantitation of anti-larval antibodies by indirect immunofluorescence. Both responses wane with time after vaccination. However subsequent challenge infection provokes immune responses of classical anamnestic character, being both more rapid in appearance and of greater magnitude. Antigen responsive cells appear in lymph nodes draining the challenge site within 24 hours after infection. Both circulating anti-schistosomulum surface antibodies as well as cytophilic IgE anti-worm antigen antibodies increase substantially by 1 week after challenge. All of the anamnestic circulating antibodies belong to the IgG class. Those findings support the concept that vaccine-induced resistance to Schistosoma mansoni infection involves sensitized T and B lymphocytes, and point to the possible role of post-challenge anamnestic responses in the effector mechanism of parasite killing in this model

  20. Immunohistochemical study of porcine lung lesions associated with Pasteurella multocida

    DEFF Research Database (Denmark)

    Pors, Susanne Elisabeth; Hansen, Mette Sif; Bisgaard, Magne

    2013-01-01

    Infectious bronchopneumonia is a widespread disease in modern commercial pig production and Pasteurella multocida is frequently associated with the lesions. To evaluate porcine lung lesions associated with P. multocida, populations of inflammatory cells were examined by immunohistochemistry...... by immunohistochemistry were T-lymphocytes (CD3(+), CD4(+) and CD8(+) subsets), B-lymphocytes, neutrophils, macrophages, and IgA(+), IgM(+) and IgG(+) cells. The results showed that (1) a significant increase in all inflammatory cells was found in lesions associated with P. multocida, (2) necrotic lesions had a larger....... The results show that P. multocida significantly alters the inflammatory response in the lung and that lesions associated with P. multocida display diverse inflammatory responses according to their distinct morphological pattern....

  1. Rituximab-induced neutropenia in a patient with inflammatory myopathy and systemic sclerosis overlap disease.

    Science.gov (United States)

    Akram, Qasim; Roberts, Mark; Oddis, Chester; Herrick, Arianne; Chinoy, Hector

    2016-01-01

    Rituximab (RTX) is a monoclonal chimeric antibody directed against the CD20 antigen of B lymphocytes. Late onset neutropenia (LON) is a recognised complication of rituximab usually occurring 4 weeks after the last dose and is reported in both haematological and rheumatological conditions. However, it has never been described in a patient with myositis and systemic sclerosis overlap disease. We describe a case of LON in a 54-year-old man who was diagnosed with myositis and then systemic sclerosis overlap disease. It resolved within 7 days, and the patient did not suffer neutropenic sepsis or any other complications. We propose similar mechanisms for LON as described in other conditions and routine blood monitoring in such patients.

  2. Cellular and humoral responses in liver of cattle and buffaloes infected with a single dose of Fasciola gigantica.

    Science.gov (United States)

    Molina, Elizabeth C; Skerratt, Lee F

    2005-07-15

    The cellular components of the hepatic inflammatory infiltrate in cattle and buffaloes infected with a single dose of 1000 Fasciola gigantica were analysed by immunohistochemistry and histology. T and B lymphocytes, plasma cells, eosinophils and mast cells were present in the hepatic lesions. It is proposed that both cellular and humoral immune responses were induced in the liver of cattle and buffaloes during infection with F. gigantica probably by antigens released by the developing flukes and by damage caused by the flukes during their migration in the liver. The local T cell response differed between these animals, with the response decreasing after 3 weeks post-infection in cattle in contrast to a gradually increasing response in buffaloes. Difference in the T cell response between cattle and buffaloes may be related to their differences in resistance and resilience to infection with F. gigantica.

  3. Signaling through intercellular adhesion molecule 1 (ICAM-1) in a B cell lymphoma line

    DEFF Research Database (Denmark)

    Holland, J; Owens, T

    1997-01-01

    Intercellular adhesion molecule 1 (ICAM-1) (CD54) is an adhesion molecule of the immunoglobulin superfamily. The interaction between ICAM-1 on B lymphocytes and leukocyte function-associated antigen 1 on T cells plays a major role in several aspects of the immune response, including T-dependent B...... cell activation. While it was originally believed that ICAM-1 played a purely adhesive role, recent evidence suggests that it can itself transduce biochemical signals. We demonstrate that cross-linking of ICAM-1 results in the up-regulation of class II major histocompatibility complex, and we...... investigate the biochemical mechanism for the signaling role of ICAM-1. We show that cross-linking of ICAM-1 on the B lymphoma line A20 induces an increase in tyrosine phosphorylation of several cellular proteins, including the Src family kinase p53/p56(lyn). In vitro kinase assays showed that Lyn kinase...

  4. PATHOGENESIS OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE

    Directory of Open Access Journals (Sweden)

    Snezana Cekic

    2006-01-01

    Full Text Available Chronic obstructive pulmonary disease (COPD is an obstructive pulmonary disorder which is characterized by limitation of expiratory airflow that is not fully reversible. The airflow limitation is usually progressive and is associated with an abnormal inflammatory response of the lungs to noxious particles or gases, primarily caused by cigarette smoking. The inflammatory process associated with COPD is characterized by increased number of activated alveolar macrophages, neutrophils, CD8+ cytotoxic T lymphocytes, B lymphocytes and CD4+ T lymphocytes, and the release of numerous inflammatory mediators (leukotrienes, cytokines, growth factors, chemokines, oxidants and proteases. Chronic inflammation causes remodeling of the small airways with the luminal obstruction due to increased mucus production and thickened walls due to edema and collagen formation that cause fibrosis and narrowing of small airways. Persistent inflammation also leads to destruction of lung tissue, loss of alveolar attachment to the small airways, and decreased lung elastic recoil. Although COPD affects the lungs, it also produces significant systemic consequences.

  5. Research on Trypanosoma cruzi and Analysis of Inflammatory Infiltrate in Esophagus and Colon from Chronic Chagasic Patients with and without Mega

    Directory of Open Access Journals (Sweden)

    Eliângela de Castro Côbo

    2012-01-01

    Full Text Available To compare parasitism and inflammatory process in esophagus and colon from chronic chagasic patients, immunohistochemistry was carried out to research for T. cruzi and to evaluate the inflammatory infiltrate in the muscular and myenteric plexus in 39 esophagi (20 with and 19 without megaesophagus and 50 colons (25 with and 25 without megacolon. The frequency of T. cruzi in megaesophagus was 20%, and in megacolon it was 4%. No amastigotes were found in organs without mega; considering the total of esophagi (with and without mega, the frequency of T. cruzi would be 10% and 2% in the colon. Myositis and ganglionitis were more frequent and intense in organs with mega compared to those without mega, and in esophagus compared to colon. Qualitatively, inflammatory infiltration in esophagus and colon, with or without mega, was similar, consisting predominantly of T lymphocytes (CD3+, scarce macrophages (CD68+, and rare B lymphocytes (CD20+.

  6. B-cell-rich T-cell lymphoma associated with Epstein-Barr virus-reactivation and T-cell suppression following antithymocyte globulin therapy in a patient with severe aplastic anemia

    Directory of Open Access Journals (Sweden)

    Nobuyoshi Hanaoka

    2015-09-01

    Full Text Available B-cell lymphoproliferative disorder (B-LPD is generally characterized by the proliferation of Epstein-Barr virus (EBV-infected B lymphocytes. We here report the development of EBV-negative B-LPD associated with EBV-reactivation following antithymocyte globulin (ATG therapy in a patient with aplastic anemia. The molecular autopsy study showed the sparse EBV-infected clonal T cells could be critically involved in the pathogenesis of EBV-negative oligoclonal B-LPD through cytokine amplification and escape from T-cell surveillances attributable to ATG-based immunosuppressive therapy, leading to an extremely rare B-cell-rich T-cell lymphoma. This report helps in elucidating the complex pathophysiology of intractable B-LPD refractory to rituximab.

  7. [Immunological changes in common vitiligo].

    Science.gov (United States)

    Vignale, R; Paciel, J; Calandria, L

    1988-01-01

    Three theories have been mentioned so as to explain vitiligo: normal, autocytotoxic and autoimmune. In this work we study the cellular immune elements in normal vitiligo. Concerning the skin, there is an increase of Langerhans cells (p less than 0.001) en its activation (DR+) (p less than 0.001). Regarding the blood, there is an increase of T cytotoxic lymphocytes (p less than 0.001), T activated lymphocytes (DR+) (p less than 0.001) and B lymphocytes (p less than 0.01). Total T lymphocytes and T cooperators (CD4+) are not increased. These results suggest that immune mechanisms mediated by T cytotoxic lymphocytes may be the cause of the melanocytes destruction in normal vitiligo.

  8. Possibilities and tasks of ray hematology in the radiation treatment of mamma carcinomas

    International Nuclear Information System (INIS)

    Mozsa, Sz.

    1980-01-01

    The hematologic implications the ray treatment of mamma carcinomas are outlined. The main lines of the evolution of the problem, the causes of the increasing interest in radiation hematology as well as the pathophysiological bases of clinical phenomena are discussed. Also, the more detailed hematological clinical characteristics, the critical peripheric values, the problem of the local inactivation bone marrow dose, and finally, the problems of the cell reserves and the provocative methods are dealt with. Because of its theoretical importance the kinetic problems of the T/B-lymphocytes are discussed. The most important factors of the chemo and hormone therapy and the laboratory examinations and the principles of general radiation hematology are also reviewed. (N.I.)

  9. Further studies of immunoglobulin synthesis by guinea-pig leukaemic lymphocytes

    International Nuclear Information System (INIS)

    Hough, D.W.; Chapple, J.C.; Stevenson, F.K.; Stevenson, G.T.

    1978-01-01

    The L 2 C leukaemia is a B-lymphocytic neoplasm of strain 2 guinea-pigs maintained by passaging in vivo. It synthesizes μ and lambda immunoglobulin chains. These combine to form monomeric (7S) IgM molecules which are inserted into the plasma membrane. From here they are shed as monomeric IgM and as a species of higher molecular weight which has not been further defined. The synthesis of lambda chain is in excess of that required for the IgM molecule, the surplus being exported directly from the cell without any intervening phase in the plasma membrane. Quantitative estimates of synthetic rates and pool sizes for these immunoglobulin species are presented. (author)

  10. Dissecting the host response to a gamma-herpesvirus

    DEFF Research Database (Denmark)

    Doherty, P C; Christensen, Jan Pravsgaard; Belz, G T

    2001-01-01

    The murine gamma-herpesvirus 68 (MHV-68) provides a unique experimental model for dissecting immunity to large DNA viruses that persist in B lymphocytes. The analysis is greatly facilitated by the availability of genetically disrupted (-/-) mice that lack key host-response elements, and by the fact...... that the interaction between the CD8+ T cells and the virus-infected targets is partially compromised by the MHV-68 K3 protein, which inhibits antigen presentation by MHC class I glycoproteins. Immunization strategies focusing on the CD8+ T-cell response to epitopes expressed during the lytic phase of MHV-68 infection...... can limit virus replication, but are unable to prevent the establishment of latency. Other experiments with mutant viruses also suggest that there is a disconnection between lytic MHV-68 infection and latency. The massive nonspecific immunoglobulin response and the dramatic expansion of Vbeta4+ CD8+ T...

  11. [REARRANGEMENT OF THE LYMPH TISSUE IN THE MICE SPLEEN AND JEJUNUM WALL DURING THE GROUND-BASED REPRODUCTION OF THE CONDITIONS OF ANIMAL MAINTENANCE IN THE BIOSATTELITE BION-M1 MISSION].

    Science.gov (United States)

    Grigorenko, D E; Aminova, G G; Erofeeva, L M; Shenkman, B S; Ilyin, E A

    2015-01-01

    Purpose of the investigation was microscopic examination of changes in cyto architectonics of the spleen and jejunum lymph (immune) tissue in 19-20-week C57BL/6N male mice exposed to some conditions their counterparts had lived in during the 30-d Bion-M1 mission (ground experiment). Local deviations in reactions of the morphofunctional zones of these organs were found. In the spleen, reaction in the centers of lymph nodules generation or the B-lymphocytes maturation zone grows strong. Changes in the cell composition of periarterial lymph sheaths that constitute the morphological site of T-lymphocytes accumulation suggest inhibition of its functional activity. Cell composition of the jejunum wall structure implies a decline of the jejunal immune activity. Our investigation of the organs taken from the ground control mice maintained in the flight BIOS-MLZh module evidences that unceasing noise, hypokinesia, isolation, and paste-like feed weaken general immunity of laboratory animals.

  12. Detection of antibodies specific for HLA-A,B,C,DR,DQ and DP by the erythrocyte antibody rosette inhibition (EAI) and immune phagocytosis inhibition (IPI) tests.

    Science.gov (United States)

    Faust, A; Neppert, J

    1987-08-24

    Two methods for the detection of murine monoclonal antibodies against determinants of the human major histocompatibility complex (MHC) were evaluated. These methods are based upon the function of Fc receptors; the erythrocyte antibody rosette inhibition test (EAI test) using B-lymphocytes and the immune phagocytosis inhibition test (IPI test) using monocytes. Compared to the EAI test the IPI test was technically easier and gave better discrimination between positive and negative results. The inhibition by antibodies of monomorphic class II MHC or polymorphic HLA-DR antigens was stronger in the IPI than in the EAI test. Antibodies against HLA-DQ and DP antigens evoked inhibition only using the EAI test. Using IgG derived from placenta in different dilutions the detection of its anti-HLA antibodies was more readily achieved in the IPI test than in the EAI test.

  13. Mouse B- and T-cell colony formation in vitro. I. Separation of colony-promoting and -inhibiting activities in concanavalin A rat spleen conditioned medium

    DEFF Research Database (Denmark)

    Claësson, M H; Nissen, Mogens Holst; Röpke, C

    1984-01-01

    Rat spleen cell cultures exposed for 24 h to concanavalin A (Con A-CM) contain, in addition to interleukin 2 (IL-2), factors that promote colony formation in vitro by mouse T cells (TCPA) and B cells (BCPA). TCPA and BCPA are separable on a Sephadex G-75 column. TCPA has a molecular weight of 15......,000 daltons and shows the same elution profile as IL-2. Absorption studies with Con A-activated T cells suggested that TCPA and IL-2 are the same entity. BCPA has an apparent molecular weight of 45,000 daltons and stimulates colony formation by B lymphocytes seeded at very low cell density (10(4) - 5 X 10......,000-130,000 and about 50,000, respectively. Because of the specificity, simplicity and sensitivity of B and T colony formation these assay systems should be valuable tools for in vitro testing of biological activities regulating the immune system....

  14. Influence of Dendritic Cells on B-Cell Responses during HIV Infection

    Directory of Open Access Journals (Sweden)

    Johanne Poudrier

    2012-01-01

    Full Text Available Dendritic cells (DCs modulate B-cell differentiation, activation, and survival mainly through production of growth factors such as B lymphocyte stimulator (BLyS/BAFF. DC populations have been reported to be affected in number, phenotype and function during HIV infection and such alterations may contribute to the dysregulation of the B-cell compartment. Herein, we reflect on the potential impact of DC on the pathogenesis of HIV-related B cell disorders, and how DC status may modulate the outcome of mucosal B cell responses against HIV, which are pivotal to the control of disease. A concept that could be extrapolated to the overall outcome of HIV disease, whereby control versus progression may reside in the host’s capacity to maintain DC homeostasis at mucosal sites, where DC populations present an inherent capacity of modulating the balance between tolerance and protection, and are amongst the earliest cell types to be exposed to the virus.

  15. A review of immunological and infectious disease studies at ABCC-RERF

    International Nuclear Information System (INIS)

    Finch, S.C.

    1980-11-01

    This report reviews the results of 20 years of ABCC-RERF studies for evidence of abnormalities in the exposed atomic bomb survivors relating to infectious, inflammatory, or immunologic disorders. Relatively few definitive immunologic investigations have been conducted. The findings, however, suggest possible radiationrelated impairment of the antibody response to certain type A influenza viruses in the in utero exposed children and an increased prevalence rate of hepatitis associated antigen in the serums of heavily exposed persons in comparison to their controls. Preliminary studies indicate that the T to B lymphocyte ratio and the phytohemagglutinin responsiveness of the T lymphocytes of the heavily exposed persons, especially those of older age, are moderately depressed. Observation in the Adult Health Study population have shown little evidence of increased infectious or inflammatory disease in the exposed survivors. (author)

  16. Severe combined immunodeficiency in a Fell pony foal.

    Science.gov (United States)

    Jelìnek, F; Faldyna, M; Jasurkova-Mikutova, G

    2006-03-01

    Five days after birth of a viable Fell pony filly, yellow watery diarrhoea appeared without any signs of systemic disease. Four days later the diarrhoea ceased. On 11th day, the animal showed apathy, and a few days later, the foal was very lethargic, suffered from muscular weakness and severe watery diarrhoea that reappeared. The illness did not respond to therapy. At the age of 21 days the filly spontaneously died under symptoms of intestinal colic and pneumonia. Haematological examinations revealed lower numbers of erythrocytes as well as non-selective lymphopenia. Phagocytic activity was slightly increased, lymphocyte activity was inhibited. Histopathology showed severe alteration of the lymphatic organs. T and B lymphocytes and antigen-presenting macrophages were not arranged in characteristic areas, and the quantity of these cells was lower than would be expected. Histopathological changes in lymphatic organs resembled those described in the literature as severe combined immunodeficiency.

  17. Lectin binders

    International Nuclear Information System (INIS)

    Rudiger, H.; Gebauer, G.; Gansera, R.; Schurz, H.; Schimpl, A.

    1982-01-01

    Lectins are widely distributed in the plant kingdom, many of them being well characterized in their chemical structure and the effects they have on alien biological systems such as erythrocytes or lymphocytes. The biological function of plant lectins remains speculative. We therefore inspected plant extracts from components which might bind specifically to the lectin from the respective plant. Single proteins (lectin binders) could be isolated from each plant extract. The interaction of these proteins with lectins was demonstrated and qualified by several methods. Similar to the lectins, the lectin binders are localized in the cytoplasm in contrast to them, however, they persist during germination and plant growth. Their precise role in the plant is not known, but they are likely to be associated with lectins not only in vitro but also in vivo. They also interact with alien cells, and are able to stimulate mitosis in murine lymphocytes. Some lectin binders act specifically on B lymphocytes, leaving T cells uninfluenced

  18. Applying mass spectrometry based proteomic technology to advance the understanding of multiple myeloma

    Directory of Open Access Journals (Sweden)

    Evans Ken

    2010-04-01

    Full Text Available Abstract Multiple myeloma (MM is the second most common hematological malignancy in adults. It is characterized by clonal proliferation of terminally differentiated B lymphocytes and over-production of monoclonal immunoglobulins. Recurrent genomic aberrations have been identified to contribute to the aggressiveness of this cancer. Despite a wealth of knowledge describing the molecular biology of MM as well as significant advances in therapeutics, this disease remains fatal. The identification of biomarkers, especially through the use of mass spectrometry, however, holds great promise to increasing our understanding of this disease. In particular, novel biomarkers will help in the diagnosis, prognosis and therapeutic stratification of MM. To date, results from mass spectrometry studies of MM have provided valuable information with regards to MM diagnosis and response to therapy. In addition, mass spectrometry was employed to study relevant signaling pathways activated in MM. This review will focus on how mass spectrometry has been applied to increase our understanding of MM.

  19. Methods for examination of antigenicity of heterogeneous polymerized hemoglobin

    International Nuclear Information System (INIS)

    Chen Lin; Zhang Yadong; Bu Fengrong; Zhang Jingang

    2004-01-01

    Objective: To choose and establish the methods for examination of heterogeneous polymerized hemoglobin in order to offer the reference for evaluating the antigenicity of heterogeneous polymerized hemoglobin against human. Methods: Antigenicity of heterogeneous polymerized hemoglobin was examined for hypersensitivity, cell-mediated immunity reaction, humoral immunity reaction and cross-reaction of antigen. Results: The rabbit and guinea pig did not give rise to hypersensitivity. In immunized rabbits, the level of serum total IgG was normal, but the level of serum specific IgG was high. The examination of B lymphocytes showed that there was no significant difference (P>0.05) in comparison with control. Cross-reaction of antigen proved that bovine hemoglobin had cross-reaction with human hemoglobin. Suggesting that they may be homologous, the level of the serum specific antibody is high in the immunized animal. According to the immunology theories, the polymerized hemoglobin has antigenicity. (authors)

  20. Sustained virologic response following HCV eradication in two brothers with X-linked agammaglobulinaemia.

    LENUS (Irish Health Repository)

    Houlihan, Diarmaid D

    2009-08-21

    X-linked agammaglobulinaemia (XLA) is a humoral immunodeficiency syndrome characterized from childhood by the absence of circulating B lymphocytes, absent or reduced levels of serum immunoglobulin and recurrent bacterial infections. For many affected patients, regular treatment with immunoglobulin is life saving. Hepatitis C viral (HCV) infection acquired through contaminated blood products is widely described in this patient cohort. The natural history of HCV infection in patients with XLA tends to follow a more rapid and aggressive course compared to immunocompetent individuals. Furthermore, standard anti-viral therapy appears to be less efficacious in this patient cohort. Here we report the cases of two brothers with XLA who contracted HCV through contaminated blood products. They were treated with a six month course of Interferon alpha-2b and Ribavirin. We report a sustained virologic response five years after completing treatment.

  1. Primary cerebellar lymphoma with Hodgkin lymphoma-like morphology in a cat.

    Science.gov (United States)

    Yoshino, Yuka; Chambers, James K; Nakamori, Taichi; Goto-Koshino, Yuko; Nishigaki, Kazuo; Tsujimoto, Hajime; Matsuki, Naoaki; Nakayama, Hiroyuki; Uchida, Kazuyuki

    2017-09-01

    A 4-y-old cat exhibited neurologic signs such as wobbling, right head tilt, and intention tremor, and MRI revealed a mass in the cerebellum. The cat died 5 mo after initial presentation, and no neoplastic lesions, other than the cerebellar mass, were observed at autopsy. Histologically, large atypical cells resembling Hodgkin cells, with single large inclusion-like nucleoli, and those resembling Reed-Sternberg cells, with symmetrically arranged nuclei, had infiltrated the left side of the cerebellum and were admixed with small lymphocytes. These atypical cells were positive for feline leukemia virus (FeLV), CD20, BLA36, vimentin, p16, p53, and Pax5, and negative for CD3, CD79a, and Iba1 by immunohistochemistry. Multiplex PCR for immunoglobulin heavy-chain gene rearrangement revealed monoclonal proliferation of B-lymphocytes. We describe this feline primary cerebellar B-cell lymphoma that displayed Hodgkin lymphoma-like tumor cells with FeLV protein expression.

  2. Physical linkage of a human immunoglobulin heavy chain variable region gene segment to diversity and joining region elements

    International Nuclear Information System (INIS)

    Schroeder, H.W. Jr.; Walter, M.A.; Hofker, M.H.; Ebens, A.; Van Dijk, K.W.; Liao, L.C.; Cox, D.W.; Milner, E.C.B.; Perlmutter, R.M.

    1988-01-01

    Antibody genes are assembled from a series of germ-line gene segments that are juxtaposed during the maturation of B lymphocytes. Although diversification of the adult antibody repertoire results in large part from the combinatorial joining of these gene segments, a restricted set of antibody heavy chain variable (V H ), diversity (D H ), and joining (J H ) region gene segments appears preferentially in the human fetal repertoire. The authors report here that one of these early-expressed V H elements (termed V H 6) is the most 3' V H gene segment, positioned 77 kilobases on the 5' side of the J H locus and immediately adjacent to a set of previously described D H sequences. In addition to providing a physical map linking human V H , D H , and J H elements, these results support the view that the programmed development of the antibody V H repertoire is determined in part by the chromosomal position of these gene segments

  3. Postoperative radiation therapy and adjuvant chemoimmunotherapy in breast cancer. Aspects of timing and immune competence

    Energy Technology Data Exchange (ETDEWEB)

    Klefstroem, P.; Nuortio, L.; Taskinen, E.

    The effects of radiation therapy and adjuvant chemoimmunotherapy on the immune competence of patients with breast cancer were investigated. The tests performed included intradermal tuberculin tests, T- and B-lymphocyte counts, and lymphocyte blast transformation tests; phytohemagglutinin (PHA), concanavalin A (ConA) and pokeweed mitogen (PMW) were used as mitogens. Enhancement in lymphocyte proliferative response to mitogenic stimulation by PHA and PMW was seen in patients after 3 courses of chemotherapy + levamisole, whereas irradiation given after chemotherapy caused long-lasting depression in response to PHA and PWM (not significant). T-lymphocyte counts were also lower after irradiation than after chemoimmunotherapy. Clinically, the 16 patients treated with radiation therapy after chemotherapy exhibited a higher recurrence rate than the 24 patients treated first by irradiation. Enhanced reactivity to tuberculin tests occurred generally in patients receiving a planned treatment including irradiation, chemotherapy (5-fluorouracil, doxorubicin, cyclophosphamide) and levamisole. Enhancement of reactivity was seen more often in patients who had not relapsed.

  4. ZAP-70 and p72syk are signaling response elements through MHC class II molecules

    DEFF Research Database (Denmark)

    Kanner, S B; Grosmaire, L S; Blake, J

    1995-01-01

    Ligation of major histocompatibility complex (MHC) class II antigens expressed on antigen-activated human CD4+ T-lymphocytes induces early signal transduction events including the activation of tyrosine kinases, the tyrosine phosphorylation of phospholipase-C gamma 1 and the mobilization...... of intracellular calcium. Similar responses have been observed in B-cells following stimulation of MHC class II molecules, including the increased production of intracellular cAMP. In this report, we demonstrate that the ZAP-70 tyrosine kinase is a responsive signaling element following cross-linking of HLA...... by herbimycin A. MHC class II ligation on B-lymphocytes resulted in cell death, which was both qualitatively distinct from Fas-induced apoptosis and partially protected by herbimycin A pretreatment. Thus, ligation of MHC class II molecules expressed on human lymphocytes stimulates the ZAP-70/p72syk family...

  5. Allelic exclusion of IgH through inhibition of E2A in a VDJ recombination complex.

    Science.gov (United States)

    Hauser, Jannek; Grundström, Christine; Grundström, Thomas

    2014-03-01

    A key feature of the immune system is the paradigm that one lymphocyte has only one Ag specificity that can be selected for or against. This requires that only one of the alleles of genes for AgR chains is made functional. However, the molecular mechanism of this allelic exclusion has been an enigma. In this study, we show that B lymphocytes with E2A that cannot be inhibited by calmodulin are dramatically defective in allelic exclusion of the IgH locus. Furthermore, we provide data supporting that E2A, PAX5, and the RAGs are in a VDJ recombination complex bound to key sequences on the Igh gene. We show that pre-BCR activation releases the VDJ recombination complex through calmodulin binding to E2A. We also show that pre-BCR signaling downregulates several components of the recombination machinery, including RAG1, RAG2, and PAX5, through calmodulin inhibition of E2A.

  6. Three faces of recombination activating gene 1 (RAG1) mutations.

    Science.gov (United States)

    Patiroglu, Turkan; Akar, Himmet Haluk; Van Der Burg, Mirjam

    2015-12-01

    Severe combined immune deficiency (SCID) is a group of genetic disorder associated with development of T- and/or B-lymphocytes. Recombination-activating genes (RAG1/2) play a critical role on VDJ recombination process that leads to the production of a broad T-cell receptor (TCR) and B-cell receptor (BCR) repertoire in the development of T and B cells. RAG1/2 genes mutations result in various forms of primary immunodeficiency, ranging from classic SCID to Omenn syndrome (OS) to atypical SCID with such as granuloma formation and autoimmunity. Herein, we reported 4 patients with RAG1 deficiency: classic SCID was seen in two patients who presented with recurrent pneumonia and chronic diarrhoea, and failure to thrive. OS was observed in one patient who presented with chronic diarrhoea, skin rash, recurrent lower respiratory infections, and atypical SCID was seen in one patient who presented with Pyoderma gangrenosum (PG) and had novel RAG1 mutation.

  7. Production and characterization of monoclonal antibodies against α-globin chain-containing human hemoglobins for detecting α-thalassemia disease.

    Science.gov (United States)

    Pakdeepak, Kanet; Pata, Supansa; Chiampanichayakul, Sawitree; Kasinrerk, Watchara; Tatu, Thanusak

    2016-01-01

    Monoclonal antibodies against α-globin containing human Hbs, named AMS-Alpha1 and AMS-Alpha 2, were produced by the hybridoma technique using spleen cells enriched by the newly developed B lymphocyte enrichment protocol. These two monoclonal antibodies were of IgM class, reacting to only intact form of human Hbs A, A2, E, and F, which contain α-globin chain. By the indirect ELISA, the AMS-Alpha1 and AMS-Alpha 2 quantified less amount of α-globin chain containing hemoglobins in HbH disease than the SEA-α thalassemia 1 carriers and normal individuals. It was thus anticipated that these monoclonal antibodies can be used for detecting Hb Bart's hydrops fetalis in which no α-globin chain is produced.

  8. [Sensitivity of the splenic immunocompetent cells of mice with different genotypes to the action of alkylating agents].

    Science.gov (United States)

    Pevnitskiĭ, L A; Telegin, L Iu; Ir, K N

    1985-08-01

    It has been established in experiments in vitro that splenocytes of DBA/2GSto mice are more sensitive to the immunosuppressant action of the alkylating agents (cyclophosphamide, sarcolysine and thiophosphamide) than splenocytes of BALB/cGLacSto mice. Splenocytes of C3H/SnRap mice exhibit and intermediate type of sensitivity. T-lymphocytes of the spleen of BALB/cGLacSto and DBA/2GSto mice are more sensitive in vitro to the action of active metabolites of cyclophosphamide as compared to B-lymphocytes, with both types of the cells of DBA/2GSto mice being affected to a greater extent than the cells of BALB/cGLacSto mice.

  9. The association of exosomes with lymph nodes.

    Science.gov (United States)

    Hood, Joshua L

    2017-07-01

    Cells produce extracellular nanovesicles known as exosomes that transport information between tissue microenvironments. Exosomes can engage and regulate the function of various immune cell types facilitating both normal and pathological processes. It follows that exosomes should also associate with lymph nodes containing immune cells. Herein, data derived from investigations that incorporate experiments pertaining to the trafficking of exosomes to lymph nodes is reviewed. Within lymph nodes, direct evidence demonstrates that exosomes associate with dendritic cells, subcapsular sinus macrophages, B lymphocytes and stromal cells. Interactions with endothelial cells are also likely. The functional significance of these associations depends on exosome type. Continued investigations into the relationship between exosomes and lymph nodes will further our understanding of how exosomes regulate immune cells subsets and may serve to inspire new exosome based therapeutics to treat a variety of diseases. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Expression of immunoglobulin gene with classical V-(D)-J rearrangement in mouse testis and epididymis.

    Science.gov (United States)

    Huang, Jing; Zhang, Li; Ma, Teng; Zhang, Pei; Qiu, Xiaoyan

    2009-04-01

    Immunoglobulin (Ig) molecules have thus far been found only to be produced by differentiated B lymphocytes. As we know, immune privilege in the normal adult mouse testis exists to make these privileged sites generally free of patrolling immune cells and Igs. However, in this study, the expression of Ig in normal adult mouse testis and epididymis was detected. First, by IHC, a strong pattern of Ig expression was detected in the spermatogenic cells of adult mouse testis at different development stages. Second, by Western blot analysis, different strong bands of Igs in mouse testicular spermatogenic cells and epididymal epithelial cell extract were recognized using specific antibodies against IgG. More importantly, by ISH and cell sorting-related RT-PCR, rearranged Ig gamma chain and kappa chain transcripts were expressed in testicular spermatogenic cells and epididymal epithelial cells. These results suggested that Ig in testis and epididymis was mainly produced by adult mouse testicular spermatogenic cells and epididymal epithelial cells.

  11. Granulomatous-lymphocytic interstitial lung disease as the first manifestation of common variable immunodeficiency.

    Science.gov (United States)

    Tashtoush, Basheer; Memarpour, Roya; Ramirez, Jose; Bejarano, Pablo; Mehta, Jinesh

    2018-01-01

    Common variable immunodeficiency (CVID) is one of the most common primary immunodeficiencies, which is characterized by reduced serum immunoglobulin levels and B-lymphocyte dysfunction. There are many clinical manifestations of this disease, the most common of which are recurrent respiratory tract infections. Among the most recently recognized autoimmune manifestation of CVID is a disease described as granulomatous-lymphocytic interstitial lung disease (GLILD), where CVID coexists with a small airway lymphoproliferative disorder, mimicking follicular bronchiolitis, or lymphocytic interstitial pneumonitis (LIP) on histology specimens. We herein describe the clinical and radiological features of GLILD in a 55-year-old woman where the diagnosis of CVID was actively pursued and eventually confirmed after her lung biopsy showed characteristic features of GLILD. The patient had dramatic response to treatment with IVIG and corticosteroids for 3 months followed by Mycophenolate mofetil for maintenance therapy. © 2016 John Wiley & Sons Ltd.

  12. CD4-regulatory cells in COPD patients

    DEFF Research Database (Denmark)

    Smyth, Lucy J C; Starkey, Cerys; Vestbo, Jørgen

    2007-01-01

    BACKGROUND: The numbers of airway CD8 and B lymphocytes are increased in COPD patients, suggesting an autoimmune process. CD4-regulatory T cells control autoimmunity but have not been studied in patients with COPD. OBJECTIVE: To compare T-regulatory cell numbers in the BAL from COPD patients......, smokers with normal lung function, and healthy nonsmokers (HNS). METHODS: BAL and peripheral blood mononuclear cell (PBMC) samples were obtained from 26 COPD patients, 19 smokers, and 8 HNS. Flow cytometry was performed for regulatory phenotypic markers. RESULTS: COPD patients had increased BAL CD8...... numbers compared to smokers and HNS. CD4 numbers were similar between groups. There was increased BAL CD4CD25(bright) expression in smokers (median 28.8%) and COPD patients (median 23.1%) compared to HNS (median 0%). Increased FoxP3 expression was confirmed in BAL CD4CD25(bright) cells. BAL CD4CD25 cells...

  13. Chronic stress, leukocyte subpopulations, and humoral response to latent viruses

    Energy Technology Data Exchange (ETDEWEB)

    McKinnon, W.; Weisse, C.S.; Reynolds, C.P.; Bowles, C.A.; Baum, A. (Uniformed Services Univ. of the Health Sciences, Bethesda, MD (USA))

    1989-01-01

    Psychological stress has been shown to affect immune system status and function, but most studies of this relationship have focused on acute stress and/or laboratory situations. The present study compared total numbers of leukocytes and lymphocyte subpopulations (determined by flow cytometry) and antibody titers to latent and nonlatent viruses among a group of chronically stressed individuals living near the damaged Three Mile Island (TMI) nuclear power plant with those of a demographically comparable control group. Urinary catecholamine and cortisol levels were also examined. Residents of the TMI area exhibited greater numbers of neutrophils, which were positively correlated with epinephrine levels. The TMI group also exhibited fewer B lymphocytes, T-suppressor/cytotoxic lymphocytes, and natural killer cells. Antibody titers to herpes simplex were significantly different across groups as well, whereas titers to nonlatent rubella virus as well as IgG and IgM levels were comparable.

  14. Chronic stress, leukocyte subpopulations, and humoral response to latent viruses

    International Nuclear Information System (INIS)

    McKinnon, W.; Weisse, C.S.; Reynolds, C.P.; Bowles, C.A.; Baum, A.

    1989-01-01

    Psychological stress has been shown to affect immune system status and function, but most studies of this relationship have focused on acute stress and/or laboratory situations. The present study compared total numbers of leukocytes and lymphocyte subpopulations (determined by flow cytometry) and antibody titers to latent and nonlatent viruses among a group of chronically stressed individuals living near the damaged Three Mile Island (TMI) nuclear power plant with those of a demographically comparable control group. Urinary catecholamine and cortisol levels were also examined. Residents of the TMI area exhibited greater numbers of neutrophils, which were positively correlated with epinephrine levels. The TMI group also exhibited fewer B lymphocytes, T-suppressor/cytotoxic lymphocytes, and natural killer cells. Antibody titers to herpes simplex were significantly different across groups as well, whereas titers to nonlatent rubella virus as well as IgG and IgM levels were comparable

  15. Non-homologous end joining mediated DNA repair is impaired in the NUP98-HOXD13 mouse model for myelodysplastic syndrome.

    Science.gov (United States)

    Puthiyaveetil, Abdul Gafoor; Reilly, Christopher M; Pardee, Timothy S; Caudell, David L

    2013-01-01

    Chromosomal translocations typically impair cell differentiation and often require secondary mutations for malignant transformation. However, the role of a primary translocation in the development of collaborating mutations is debatable. To delineate the role of leukemic translocation NUP98-HOXD13 (NHD13) in secondary mutagenesis, DNA break and repair mechanisms in stimulated mouse B lymphocytes expressing NHD13 were analyzed. Our results showed significantly reduced expression of non-homologous end joining (NHEJ)-mediated DNA repair genes, DNA Pkcs, DNA ligase4, and Xrcc4 leading to cell cycle arrest at G2/M phase. Our results showed that expression of NHD13 fusion gene resulted in impaired NHEJ-mediated DNA break repair. Copyright © 2012 Elsevier Ltd. All rights reserved.

  16. Structure of an Ebf1:DNA complex reveals unusual DNA recognition and structural homology with Rel proteins.

    Science.gov (United States)

    Treiber, Nora; Treiber, Thomas; Zocher, Georg; Grosschedl, Rudolf

    2010-10-15

    Early B-cell factor 1 (Ebf1) is a key transcriptional determinant of B-lymphocyte differentiation whose DNA-binding domain has no sequence similarity to other transcription factor families. Here we report the crystal structure of an Ebf1 dimer bound to its palindromic recognition site. The DNA-binding domain adopts a pseudoimmunoglobulin-like fold with novel topology, but is structurally similar to the Rel homology domains of NFAT and NF-κB. Ebf1 contacts the DNA with two loop-based modules and a unique Zn coordination motif whereby each Ebf1 monomer interacts with both palindromic half-sites. This unusual mode of DNA recognition generates an extended contact area that may be crucial for the function of Ebf1 in chromatin.

  17. Acquisition of Genetic Aberrations by Activation-Induced Cytidine Deaminase (AID during Inflammation-Associated Carcinogenesis

    Directory of Open Access Journals (Sweden)

    Tsutomu Chiba

    2011-06-01

    Full Text Available Genetic abnormalities such as nucleotide alterations and chromosomal disorders that accumulate in various tumor-related genes have an important role in cancer development. The precise mechanism of the acquisition of genetic aberrations, however, remains unclear. Activation-induced cytidine deaminase (AID, a nucleotide editing enzyme, is essential for the diversification of antibody production. AID is expressed only in activated B lymphocytes under physiologic conditions and induces somatic hypermutation and class switch recombination in immunoglobulin genes. Inflammation leads to aberrant AID expression in various gastrointestinal organs and increased AID expression contributes to cancer development by inducing genetic alterations in epithelial cells. Studies of how AID induces genetic disorders are expected to elucidate the mechanism of inflammation-associated carcinogenesis.

  18. Acquisition of Genetic Aberrations by Activation-Induced Cytidine Deaminase (AID) during Inflammation-Associated Carcinogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Takai, Atsushi; Marusawa, Hiroyuki, E-mail: maru@kuhp.kyoto-u.ac.jp; Chiba, Tsutomu [Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto 606-8507 (Japan)

    2011-06-22

    Genetic abnormalities such as nucleotide alterations and chromosomal disorders that accumulate in various tumor-related genes have an important role in cancer development. The precise mechanism of the acquisition of genetic aberrations, however, remains unclear. Activation-induced cytidine deaminase (AID), a nucleotide editing enzyme, is essential for the diversification of antibody production. AID is expressed only in activated B lymphocytes under physiologic conditions and induces somatic hypermutation and class switch recombination in immunoglobulin genes. Inflammation leads to aberrant AID expression in various gastrointestinal organs and increased AID expression contributes to cancer development by inducing genetic alterations in epithelial cells. Studies of how AID induces genetic disorders are expected to elucidate the mechanism of inflammation-associated carcinogenesis.

  19. Occurrence and Tissue Distribution of Porcine Circovirus Type 2 Identified by Immunohistochemistry in Danish Finishing Pigs at Slaughter

    DEFF Research Database (Denmark)

    Hansen, Mette Sif; Pors, S. E.; Bille-Hansen, Vivi

    2010-01-01

    or more tissues of 61% of the pigs were positive for PCV2 antigen. Up to 78% of the pigs had mild lymphoid depletion, indistinct lymphoid follicles and/or histiocytic Infiltration of the lymph nodes, but these lesions were not associated with PCV2. No association was found between the presence of lung...... in the early post-weaning period and are also recognized in finishing pigs of 12-19 weeks of I e. The aim of the present study was to assess Hie role of PCV2 infection in disease of finishing pigs. Accordingly, the occurrence and tissue distriubution of PCV2 was examined in Danish finishing pigs at the time...... common and localized to the centres of lymphoid follicles, Corresponding to the morphology and distribution of FDCs. This observation may be interpreted to suggest that PCV2 may Interact with FDCs to cause depletion of B lymphocytes. Alternatively, the FDCs may be a reservoir of infective PCV2...

  20. Activation of vestibule-associated lymphoid tissue in localized provoked vulvodynia.

    Science.gov (United States)

    Tommola, Päivi; Bützow, Ralf; Unkila-Kallio, Leila; Paavonen, Jorma; Meri, Seppo

    2015-04-01

    Localized provoked vulvodynia (LPV) may have inflammatory etiology. We wanted to find out whether the cell-mediated immune system becomes activated in the vestibular mucosa in LPV. This was a controlled cross-sectional study. Vestibular mucosal specimens were obtained from 27 patients with severe LPV and 15 controls. Detailed clinical history of the patients was obtained. For immunohistochemistry, antibodies against CD3 (T cells), CD20 (B cells), IgA (mucosal plasma cells), CD163 (dendritic cells [DCs]), CD68 (macrophages), and CD117 (mast cells) were employed. Mann-Whitney U test and χ(2) test were used for statistical analyses. More B lymphocytes and mature mucosal IgA-plasma cells were found in patients than in controls (P associated lymphoid tissue analogous to mucosa-associated lymphoid tissue. Vestibule-associated lymphoid tissue may emerge as a response to local infection or inflammation in LPV. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Epstein–Barr virus particles induce centrosome amplification and chromosomal instability

    Science.gov (United States)

    Shumilov, Anatoliy; Tsai, Ming-Han; Schlosser, Yvonne T.; Kratz, Anne-Sophie; Bernhardt, Katharina; Fink, Susanne; Mizani, Tuba; Lin, Xiaochen; Jauch, Anna; Mautner, Josef; Kopp-Schneider, Annette; Feederle, Regina; Hoffmann, Ingrid; Delecluse, Henri-Jacques

    2017-01-01

    Infections with Epstein–Barr virus (EBV) are associated with cancer development, and EBV lytic replication (the process that generates virus progeny) is a strong risk factor for some cancer types. Here we report that EBV infection of B-lymphocytes (in vitro and in a mouse model) leads to an increased rate of centrosome amplification, associated with chromosomal instability. This effect can be reproduced with virus-like particles devoid of EBV DNA, but not with defective virus-like particles that cannot infect host cells. Viral protein BNRF1 induces centrosome amplification, and BNRF1-deficient viruses largely lose this property. These findings identify a new mechanism by which EBV particles can induce chromosomal instability without establishing a chronic infection, thereby conferring a risk for development of tumours that do not necessarily carry the viral genome. PMID:28186092

  2. A highly selective CCR2 chemokine agonist encoded by human herpesvirus 6

    DEFF Research Database (Denmark)

    Lüttichau, Hans R; Clark-Lewis, Ian; Jensen, Peter Østrup

    2003-01-01

    calcium mobilization as efficiently as the endogenous chemokine ligand CCL2 through the CCR2 receptor, whereas the virally encoded chemokine did not affect any of the other 17 human chemokine receptors tested. Mutual cross-desensitization between CCL2 and vCCL4 was demonstrated in the CCR2-transfected...... cells. The affinity of vCCL4 for the CCR2 receptor was 79 nm as determined in competition binding against radioactively labeled CCL2. In the murine pre-B lymphocyte cell line L1.2 stably transfected with the CCR2 receptor, vCCL4 acted as a relatively low potency but highly efficacious chemoattractant...... being equally or more efficacious in causing cell migration than CCL2 and CCL7 and considerably more efficacious than CCL8 and CCL13. It is concluded that human herpesvirus 6 encodes a highly selective and efficacious CCR2 agonist, which will attract CCR2 expressing cells, for example macrophages...

  3. Molecular Mechanisms Used bySalmonellato Evade the Immune System.

    Science.gov (United States)

    Bernal-Bayard, Joaquín; Ramos-Morales, Francisco

    2018-01-01

    Human and animal pathogens are able to circumvent, at least temporarily, the sophisticated immune defenses of their hosts. Several serovars of the Gram-negative bacterium Salmonella enterica have been used as models for the study of pathogen-host interactions. In this review we discuss the strategies used by Salmonella to evade or manipulate three levels of host immune defenses: physical barriers, innate immunity and adaptive immunity. During its passage through the digestive system, Salmonella has to face the acidic pH of the stomach, bile and antimicrobial peptides in the intestine, as well as the competition with resident microbiota. After host cell invasion, Salmonella manipulates inflammatory pathways and the autophagy process. Finally, Salmonella evades the adaptive immune system by interacting with dendritic cells, and T and B lymphocytes. Mechanisms allowing the establishment of persistent infections are also discussed.

  4. Molecular design of materials for cell separation.

    Science.gov (United States)

    Kataoka, K

    1988-12-01

    There has been a strong demand in biomedical sciences to isolate viable cell populations with high yield and purity. An important facet of this work was to develop new polymeric adsorbent for the separation of lymphocyte subpopulations. Based on our strategy of separating cells through their differential ionic affinity toward multiphase-structured adsorbent with ionically derivatized microdomains, a series of poly(2-hydroxyethyl methacrylate)/polyamine graft copolymers (HA copolymers) was prepared. HA copolymer columns were found to show specific adsorption affinity toward B lymphocytes, and allows for separation of B and T lymphocytes in high yield and purity with a short operating time. Separation mechanism involved in the resolution of B and T lymphocytes by HA copolymer column is discussed in this paper. Further, photo-induced desorption of cells from the adsorbent derivatized with photo-responsive functional group (azobenzene group) was demonstrated to emphasize the feasibility of photo-regulated chromatography as a novel tool in cell separation technology.

  5. Cellular and humoral immunity, mood and exam stress: the influences of self-hypnosis and personality predictors.

    Science.gov (United States)

    Gruzelier, J; Smith, F; Nagy, A; Henderson, D

    2001-08-01

    The effects of self-hypnosis training on immune function and mood were examined in medical students at exam time. Hypnosis involved relaxation and imagery directed at improved immune function and increased energy, alertness and concentration. Hypotheses were made about activated and withdrawn personality differences. Eight high and eight low hypnotically susceptible participants were given 10 sessions of hypnosis, one live and nine tape-recorded, and were compared with control subjects (N=12). CD3, CD4, CD8, CD19 and CD56 NK cells and blood cortisol were assayed. Life-style, activated vs. withdrawn temperament, arousal and anxiety questionnaires were administered. Self-hypnosis buffered the decline found in controls in NK (Pexam levels of T and B lymphocytes (P&z.Lt;0.08-Pstress in young, healthy adults have implications for illness prevention and for patients with compromised immunity.

  6. A role for NADPH oxidase in antigen presentation

    Directory of Open Access Journals (Sweden)

    Gail J Gardiner

    2013-09-01

    Full Text Available The nicotinamide adenine dinucleotide phosphate (NADPH oxidase expressed in phagocytes is a multi-subunit enzyme complex that generates superoxide (O2.-. This radical is an important precursor of hydrogen peroxide (H2O2 and other reactive oxygen species (ROS needed for microbicidal activity during innate immune responses. Inherited defects in NADPH oxidase give rise to chronic granulomatous disease (CGD, a primary immunodeficiency characterized by recurrent infections and granulomatous inflammation. Interestingly, CGD, CGD carrier status, and oxidase gene polymorphisms have all been associated with autoinflammatory and autoimmune disorders, suggesting a potential role for NADPH oxidase in regulating adaptive immune responses. Here, NADPH oxidase function in antigen processing and presentation is reviewed. NADPH oxidase influences dendritic cell (DC crosspresentation by major histocompatibility complex class I molecules (MHC-I through regulation of the phagosomal microenvironment, while in B lymphocytes, NADPH oxidase alters epitope selection by major histocompatibility complex class II molecules (MHC-II.

  7. Multiple myeloma presenting with a maxillary lesion as the first sign

    Energy Technology Data Exchange (ETDEWEB)

    Ramaiah, Kiran Kumar Kotagudda; Joshi, Vajendra; Thayi, Shilpa Ravishankar; Sathyanarayana, Pathalapate; Patil, Prashant [Dept. of Oral Medicine and Radiology, Navodaya Dental College and Hospital, Raichur (Korea, Republic of); Ahmed, Zaheer [Dept. of Public Health Dentistry, Navodaya Dental College and Hospital, Raichur (Korea, Republic of)

    2015-03-15

    Multiple myeloma is a clonal neoplastic proliferation of terminally differentiated B-lymphocytes involving the skeletal system in a multifocal fashion. Its oral manifestations are less common in the maxilla than in the mandible due to the lower amount of hemopoietic bone marrow in the maxilla. We report the case of a 50-year-old man who presented with a mass in the left maxillary alveolar region with tooth mobility. The mass had become enlarged after the teeth were extracted 15 days previously. Radiographs demonstrated multiple punched-out radiolucent lesions in the skull and pelvic region. Computed tomography images showed a soft tissue density mass in the left maxilla, eroding the floor and walls of the maxillary sinus. Although several analytical techniques were used to characterize the lesion, it was finally confirmed as multiple myeloma through immunohistochemistry.

  8. T cell precursor migration towards beta 2-microglobulin is involved in thymus colonization of chicken embryos

    DEFF Research Database (Denmark)

    Dunon, D; Kaufman, J; Salomonsen, J

    1990-01-01

    beta 2-microglobulin (beta 2m) attracts hemopoietic precursors from chicken bone marrow cells in vitro. The cell population responding to beta 2m increases during the second period of thymus colonization, which takes place at days 12-14 of incubation. The precursors from 13.5 day old embryos were...... isolated after migration towards beta 2m in vitro and shown to be able to colonize a 13 day old thymus in ovo, where they subsequently acquire thymocyte markers. In contrast these beta 2m responsive precursors did not colonize embryonic bursa, i.e. differentiate into B lymphocytes. During chicken...... embryogenesis, peaks of beta 2m transcripts and of free beta 2m synthesis can only be detected in the thymus. The peak of free beta 2m synthesis in the thymus and the increase of beta 2m responding bone marrow cells both occur concomitantly with the second wave of thymus colonization in chicken embryo, facts...

  9. Acquisition of Genetic Aberrations by Activation-Induced Cytidine Deaminase (AID) during Inflammation-Associated Carcinogenesis

    International Nuclear Information System (INIS)

    Takai, Atsushi; Marusawa, Hiroyuki; Chiba, Tsutomu

    2011-01-01

    Genetic abnormalities such as nucleotide alterations and chromosomal disorders that accumulate in various tumor-related genes have an important role in cancer development. The precise mechanism of the acquisition of genetic aberrations, however, remains unclear. Activation-induced cytidine deaminase (AID), a nucleotide editing enzyme, is essential for the diversification of antibody production. AID is expressed only in activated B lymphocytes under physiologic conditions and induces somatic hypermutation and class switch recombination in immunoglobulin genes. Inflammation leads to aberrant AID expression in various gastrointestinal organs and increased AID expression contributes to cancer development by inducing genetic alterations in epithelial cells. Studies of how AID induces genetic disorders are expected to elucidate the mechanism of inflammation-associated carcinogenesis

  10. Constitutive activation of extracellular signal-regulated kinase predisposes diffuse large B-cell lymphoma cell lines to CD40-mediated cell death

    DEFF Research Database (Denmark)

    Hollmann, C Annette; Owens, Trevor; Nalbantoglu, Josephine

    2006-01-01

    , including LCK and VAV. In addition, CD40-sensitive DLBCL cell lines also displayed constitutive activation of extracellular signal-regulated kinase (ERK) and failed to undergo apoptosis when ERK phosphorylation was inhibited. In contrast, CD40-resistant lines showed no constitutive activation of ERK......CD40 promotes survival, proliferation, and differentiation of normal B cells but can cause activation-induced cell death in malignant B lymphocytes. CD40 ligand and anti-CD40 antibodies have been used successfully to induce apoptosis in lymphoma lines both in vitro and in xenograft tumor models....... Although this makes CD40 an attractive target for antitumor therapies, the response of malignant B cells to CD40 signaling is variable, and CD40 stimulation can enhance proliferation and can increase chemoresistance in some cell lines. It would therefore be useful to identify markers that predict whether...

  11. Histopathology and immune histochemistry of red tattoo reactions. Interface dermatitis is the lead pathology, with increase in T-lymphocytes and Langerhans cells suggesting an allergic pathomechanism

    DEFF Research Database (Denmark)

    Høgsberg, T; Thomsen, B M; Serup, J

    2015-01-01

    BACKGROUND: The majority of tattoo reactions are affiliated to red pigmented areas and often suspected to be allergic in nature. A sizeable series of biopsies of such reactions has not previously been performed. The aim of this study was to type and grade epidermal and dermal changes in tattoo...... reactions to red/red nuances by microscopy and immunochemistry relevant for the assessment of a possible allergic pathomechanism. METHODS: Skin biopsies were taken from red tattoo reactions, graded by conventional microscopy and stained for T and B-lymphocytes, Langerhans cells, macrophages and tumour......-α was common. CONCLUSION: The predominant histological pattern of chronic tattoo reactions in red/red nuances is interface dermatitis. T-lymphocytes and Langerhans cells are increased suggesting an allergic pathomechanism. TNF-α may contribute to reactions. In many cases, overlapping reactive patterns were...

  12. [Marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue type (MALT lymphoma)].

    Science.gov (United States)

    Takahashi, Tsutomu; Suzumiya, Junji

    2014-03-01

    Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue type (MALT lymphoma) is a B-cell tumor thought to originate from B-lymphocytes that are normally present in the marginal zone of lymphoid follicles of the lymphoid tissue. About 50% of MALT lymphoma occurs in gastrointestinal tract. The majority of patients present with localized disease and indolent clinical progression. In localized gastric MALT lymphoma with Helicobacter pylori (HP) infection, HP eradication is recommended as first line therapy. In those without HP infection and localized non-gastric MALT lymphoma, involved field radiation therapy(IFRT) is recommended as first line therapy. Patients in advanced stage and salvage setting are managed according to the recommendations for advanced follicular lymphoma. The long-term survival rate of MALT lymphoma patients is 80-90%.

  13. Changes in number and function of the lymphocyte populations as a biological indicator for ionizing radiation

    International Nuclear Information System (INIS)

    Dehos, A.; Hinz, G.; Schwarz, E.R.

    1986-01-01

    Siegal and Siegal reported that the number of immunoglobulin producing cells, especially after higher doses of ionizing radiation on isolated mononuclear cells decreases considerably. However, if non-irradiated B cells are cultivated with irradiated (16 Gy) T cells, a significant increase of immunoglobulin production due to the non-irradiated B cells can be observed. Siegal and Siegal described a similar result when they combined and cultivated non-irradiated with irradiated mononuclear cells. The immunoglobulin producing cells decreased in a lower and increased in a higher dose range. The two results can be explained by the fact that Tg cells which act as suppressor cells are relatively sensitive to radiation while Tm cells which are helper cells in this test are relatively resistant. According to these results, B lymphocytes are the most sensitive of the lymphocyte subpopulations. The aim of the project is to clarify whether the mentioned effects are suitable for 'biological dosimetry'. (orig./MG)

  14. A progressive multifocal neurological syndrome in a 42-year-old woman.

    LENUS (Irish Health Repository)

    Cryan, Jane

    2012-02-01

    This is the case of a 42-year-old female who presented with transient dizziness. Her symptoms and signs progressed to include dysarthria, ataxia and cognitive decline over 2 years, such that she was unable to care for herself. She died 4 years after first presentation without a diagnosis. Investigations revealed a normochromic normocytic anaemia. Cerebrospinal fluid was normal. Serial computed tomography brain showed a wedge-shaped frontal infarct but no progressive changes. Examination at autopsy showed discoloration of the gray and white matter of the brain and spinal cord.Microscopy of leptomeningeal and parenchymal vessels showed they were filled with atypical B lymphocytes confined to the intravascular space with multiple infarcts in the brain, cerebellum and spinal cord. A diagnosis of intravascular B cell lymphoma was made and is discussed.

  15. Rituximab in Minimal Change Disease

    Directory of Open Access Journals (Sweden)

    Nima Madanchi

    2017-03-01

    Full Text Available Treatment with rituximab, a monoclonal antibody against the B-lymphocyte surface protein CD20, leads to the depletion of B cells. Recently, rituximab was reported to effectively prevent relapses of glucocorticoid-dependent or frequently relapsing minimal change disease (MCD. MCD is thought to be T-cell mediated; how rituximab controls MCD is not understood. In this review, we summarize key clinical studies demonstrating the efficacy of rituximab in idiopathic nephrotic syndrome, mainly MCD. We then discuss immunological features of this disease and potential mechanisms of action of rituximab in its treatment based on what is known about the therapeutic action of rituximab in other immune-mediated disorders. We believe that studies aimed at understanding the mechanisms of action of rituximab in MCD will provide a novel approach to resolve the elusive immune pathophysiology of MCD.

  16. The Influence of Allogeneic Cells on the Human T and B Cell Repertoire

    Science.gov (United States)

    van Rood, Jon J.; Claas, Frans H. J.

    1990-06-01

    Clinical transplantation is often complicated by rejection episodes, in which the immune system of the recipient reacts to the foreign transplantation (HLA) antigens on the graft. This immune response includes humoral and cellular components. In the first, B lymphocytes form antibodies to the HLA alloantigens. In the second, CD8^+ T lymphocytes recognize and react to HLA class I antigens, and CD4^+ T cells react to HLA class II antigens. The frequency and severity of these rejection episodes can be diminished by immunosuppressive drugs, HLA matching between donor and recipient, and immune modulation by blood transfusion. Effective HLA matching between donor and recipient is not always possible and often not necessary. Insight into the factors that influence the T and B cell repertoire after blood transfusion might lead to new approaches to improve graft survival.

  17. Criteria for the selection of nuclides for radioimmunotherapy

    International Nuclear Information System (INIS)

    Adelstein, S.J.; Kassis, A.I.

    1986-01-01

    This report describes many factors that need to be considered if radioimmunotherapy is to become a commonplace reality. For beta-emitting radionuclides, two physical features of importance are half-life and energy, with the latter determining the range. These features must be matched to the pharmacokinetics of the carrier and the distribution of the radionuclide, both macroscopically and microscopically. Alpha-particle emitters could be considered for cells that are readily accessible to the labeled antibody and for populations that uniformly and constantly display the targeted antigen or idiotype, e.g., trafficking cells such as T or B lymphocytes. For cells that concentrate the radioactive label, the use of low-energy electrons should be examined. If the radionuclide is translocated to the nucleus, the Auger effect can be particularly lethal because of the high LET-like biological response. 15 refs., 3 figs., 2 tabs

  18. Preliminary findings of a previously unrecognized porcine primary immunodeficiency disorder.

    Science.gov (United States)

    Ozuna, A G Cino; Rowland, R R R; Nietfeld, J C; Kerrigan, M A; Dekkers, J C M; Wyatt, C R

    2013-01-01

    Weaned pigs from a line bred for increased feed efficiency were enrolled in a study of the role of host genes in the response to infection with Porcine Reproductive and Respiratory Syndrome Virus (PRRSV). Four of the pigs were euthanatized early in the study due to weight loss with illness and poor body condition; 2 pigs before PRRSV infection and the other 2 pigs approximately 2 weeks after virus inoculation. The 2 inoculated pigs failed to produce PRRSV-specific antibodies. Gross findings included pneumonia, absence of a detectable thymus, and small secondary lymphoid tissues. Histologically, lymph nodes, spleen, tonsils, and Peyer's patches were sparsely cellular with decreased to absent T and B lymphocytes.

  19. Why do anal wounds heal adequately? A study of the local immunoinflammatory defense mechanisms.

    Science.gov (United States)

    de Paula, Pedro Roberto; Matos, Delcio; Franco, Marcello; Speranzini, Manlio Basílio; Figueiredo, Florêncio; de Santana, Ivonete Cândida Barbosa; Chacon-Silva, Marcos Augusto; Bassi, Deomir Germano

    2004-11-01

    The aim of this study was to identify the tissue defense immunoinflammatory mechanisms present in the healing process of anal region wounds resulting from hemorrhoidectomy by the open technique. Immunohistochemical techniques were applied to biopsies of anal wounds obtained on Day 0 and Day 6 after surgery from 20 patients with hemorrhoid disease to characterize and quantify macrophages, T and B lymphocytes, and natural killer cells in high-power fields (400x). These techniques were also used to identify cells showing immunoexpression of cytokines (transforming growth factor beta 1, transforming growth factor beta 2, transforming growth factor beta 3) and constitutive and induced nitric oxide synthase. Plasma cells were quantified on slides stained with hematoxylin and eosin and the presence of immunoglobulin G, immunoglobulin M, and immunoglobulin A secreting cells was investigated by direct immunofluorescence. An acute nonspecific inflammation with no lymphomononuclear-plasmacytic component was observed on Day 0. On Day 6, an inflammatory cellular infiltration rich in macrophages and lymphoplasmacytic cells was detected, which documented the participation of innate defense mechanisms and the adaptive tissue response. On Day 6, the mean number of immunoinflammatory cells were as follows: macrophages (CD68+) = 190.3; macrophages (HAM56+) = 184.3; T lymphocytes (CD3+) = 59.6; T lymphocytes (CD45RO+) = 47.7; helper T lymphocytes (CD4+) = 89.2; cytotoxic T lymphocytes (CD8+) = 29.4; B lymphocytes (CD20+) = 64.4; plasma cells = 1.7; natural killer cells (NK1+) = 12.9. Macrophages (HAM56+ and CD68+) were present in significantly higher amounts than those of the remaining ones. B lymphocytes (CD20+) predominated over T lymphocytes (CD3+), although the difference between the two cell types was not significant. Participation of the humoral immune system was characterized by the presence of immunoglobulin G-secreting cells. The cellular immune system was characterized by

  20. In vitro analog of human bone marrow from 3D scaffolds with biomimetic inverted colloidal crystal geometry.

    Science.gov (United States)

    Nichols, Joan E; Cortiella, Joaquin; Lee, Jungwoo; Niles, Jean A; Cuddihy, Meghan; Wang, Shaopeng; Bielitzki, Joseph; Cantu, Andrea; Mlcak, Ron; Valdivia, Esther; Yancy, Ryan; McClure, Matthew L; Kotov, Nicholas A

    2009-02-01

    In vitro replicas of bone marrow can potentially provide a continuous source of blood cells for transplantation and serve as a laboratory model to examine human immune system dysfunctions and drug toxicology. Here we report the development of an in vitro artificial bone marrow based on a 3D scaffold with inverted colloidal crystal (ICC) geometry mimicking the structural topology of actual bone marrow matrix. To facilitate adhesion of cells, scaffolds were coated with a layer of transparent nanocomposite. After seeding with hematopoietic stem cells (HSCs), ICC scaffolds were capable of supporting expansion of CD34+ HSCs with B-lymphocyte differentiation. Three-dimensional organization was shown to be critical for production of B cells and antigen-specific antibodies. Functionality of bone marrow constructs was confirmed by implantation of matrices containing human CD34+ cells onto the backs of severe combined immunodeficiency (SCID) mice with subsequent generation of human immune cells.