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Sample records for b-lymphocytes

  1. [Evolution and phylogeny of B lymphocytes].

    Science.gov (United States)

    Claudio-Piedras, Fabiola; Lanz-Mendoza, Humberto

    2016-01-01

    B lymphocytes are one of the most important cell types involved in the immune response of mammals. The origin and evolution of this cellular type is unknown, but the B lymphocyte bona fide appeared first in fish. In this review we analize the principal components of the immune response of invertebrates, their phylogenetic distribution and the permancence of some properties that allowed the emergence of the B lymphocyte. We started from the idea that many of the components that characterize the B lymphocyte are found distributed among the invertebrates, however, it is in the B lymphocyte, where all these components that give this type of cell its identity, converged. The actual knowledge we have in regards of the lymphocytes comes, in the most part, from physiological studies in mammals, being the mice the more representative. The origin of the B lymphocyte, its alternative mechanisms for generating receptor diversity, its immune effector response, and the generation of memory, require an evolutionary and multidisiplinary approach for its study.

  2. Spondylarthritis in the absence of B lymphocytes.

    Science.gov (United States)

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

    2008-03-01

    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 describe 2 male HLA-B27-positive patients who had active SpA despite absence of B cells. One patient developed SpA with sacroiliitis and asymmetric oligoarthritis after having been diagnosed as having severe Bruton agammaglobulinemia. Since extensive investigations excluded an infectious origin of the SpA, this case illustrates that functional B cells and/or gamma globulins are not strictly required for SpA pathogenesis. The second patient had severe axial and peripheral SpA that was treated successfully with etanercept. After discontinuation of etanercept treatment because of non-Hodgkin's B cell lymphoma, both axial and peripheral SpA symptoms relapsed rapidly, and this exacerbation of articular disease activity was not modulated by successful B cell depletion therapy for the lymphoma. Although case reports have obvious limitations, our clinical observations provide evidence that active SpA can occur in the absence of functional mature B cells and thus emphasize the need for systematic studies of the exact role and function of B lymphocytes in this disease.

  3. SUBTYPES OF B LYMPHOCYTES IN PATIENTS WITH AUTOIMMUNE HEMOCYTOPENIA

    Institute of Scientific and Technical Information of China (English)

    Li-min Xing; Hai-rong Jia; Juan Sun; Chong-li Yang; Zong-hong Shao; Rong Fu; Hong Liu; Jun Shi; Lie Bai; Mei-feng Tu; Hua-quan Wang; Zhen-zhu Cui

    2007-01-01

    Objective To investigate the quantities of bone marrow CD5+ B lymphocytes in the patients with autoimmune hemocytopenia and the relationship between quantities of CD5+ B lymphocytes and clinical or laboratorial parameters.Methods Quantities of CD5+ B lymphocytes in the bone marrow of 14 patients with autoimmune hemolytic anemia (AIHA) or Evans syndrome, 22 immunorelated pancytopenia (IRP) patients, and 10 normal controls were assayed by flow cytometry. The correlation between their clinical or laboratorial parameters and CD5+ B lymphocytes was analyzed.Results The quantity of CD5+B lymphocytes of AIHA/Evans syndrome (34. 64% ± 19. 81% ) or IRP patients (35.81% ±16.83% ) was significantly higher than that of normal controls (12.00% ±1.97% , P<0. 05). However, there was no significant difference between AIHA/Evans syndrome and IRP patients (P > 0. 05). In all hemocytopenic patients, the quantity of bone marrow CD5+ B lymphocytes showed significantly negative correlation with serum complement C3 level (r = - 0. 416, P< 0. 05). In the patients with AIHA/Evans syndrome, the quantity of bone marrow CD5+ B lymphocytes showed significantly positive correlation with serum indirect bilirubin level (r = 1. 00, P<0. 05). In Evans syndrome patients, the quantity of CD5+ B lymphocytes in bone marrow showed significantly positive correlation with platelet-associated immunoglobulin G (r = 0. 761, P< 0. 05) and platelet-associated immunoglobulin M (r = 0. 925, P< 0. 05). The quantity of CD5+ B lymphocytes in bone marrow of all hemocytopenic patients showed significantly negative correlation with treatment response (tau-b = - 0. 289, P< 0. 05), but had no correlation with colony forming unit-erythroid ( r = - 0. 205, P > 0. 05 ) or colony forming unit-granulocyte-macrophage colonies ( r = -0.214, P>0.05).Conclusions The quantity of bone marrow CD5+ B lymphocytes in the patients with autoimmune hemocytopenia significantly increases and is correlated with disease

  4. Kinetics of circulating B lymphocytes in human myeloma

    Energy Technology Data Exchange (ETDEWEB)

    Boccadoro, M.; Gavarotti, P.; Fossati, G.; Massaia, M.; Pileri, A.; Durie, B.G.

    1983-04-01

    The tritiated thymidine labeling index (LI%) of peripheral B lymphocytes was studied in eight myeloma patients using simultaneous immunofluorescence and autoradiography. The LI% values were low (0.3%-5.1%), but significantly increased as compared to normal controls. In addition, there was excellent correlation between the LI% values and myeloma disease activity: lowest LI% values were observed in remission patients and the highest at the time of relapse. Simultaneous LI% evaluation of bone marrow myeloma cells in five patients gave concordant results, indicating the same kinetic behavior in both these compartments, particularly in the relapse phase. These data indicate both that circulating B lymphocytes include the neoplastic clone and that these B lymphocytes and bone marrow myeloma cells have similar kinetics.

  5. File list: Oth.Bld.50.AllAg.B-Lymphocytes [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Bld.50.AllAg.B-Lymphocytes mm9 TFs and others Blood B-Lymphocytes SRX1287946,SR...RX217128,SRX217129,SRX217124,SRX217126 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Bld.50.AllAg.B-Lymphocytes.bed ...

  6. File list: NoD.Bld.20.AllAg.B-Lymphocytes [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  7. File list: Oth.Bld.10.AllAg.B-Lymphocytes [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Bld.10.AllAg.B-Lymphocytes mm9 TFs and others Blood B-Lymphocytes SRX316675,SRX...1091121,SRX1091120,SRX217131,SRX148805 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Bld.10.AllAg.B-Lymphocytes.bed ...

  8. File list: DNS.Bld.10.AllAg.B-Lymphocytes [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.Bld.10.AllAg.B-Lymphocytes mm9 DNase-seq Blood B-Lymphocytes SRX148843,SRX14884...0,SRX188641,SRX148844,SRX148841,SRX191048,SRX037912,SRX148845,SRX148846,SRX148842 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/DNS.Bld.10.AllAg.B-Lymphocytes.bed ...

  9. File list: ALL.Bld.10.AllAg.B-Lymphocytes [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  10. File list: DNS.Bld.10.AllAg.B-Lymphocytes [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  11. File list: DNS.Bld.50.AllAg.B-Lymphocytes [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  12. File list: ALL.Bld.05.AllAg.B-Lymphocytes [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  13. File list: ALL.Bld.50.AllAg.B-Lymphocytes [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  14. File list: Pol.Bld.05.AllAg.B-Lymphocytes [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Bld.05.AllAg.B-Lymphocytes hg19 RNA polymerase Blood B-Lymphocytes SRX170357 ht...tp://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.Bld.05.AllAg.B-Lymphocytes.bed ...

  15. File list: InP.Bld.50.AllAg.B-Lymphocytes [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  16. File list: Unc.Bld.05.AllAg.B-Lymphocytes [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Bld.05.AllAg.B-Lymphocytes mm9 Unclassified Blood B-Lymphocytes SRX398229,SRX20...5602,SRX186173 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Bld.05.AllAg.B-Lymphocytes.bed ...

  17. File list: InP.Bld.20.AllAg.B-Lymphocytes [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  18. File list: DNS.Bld.50.AllAg.B-Lymphocytes [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.Bld.50.AllAg.B-Lymphocytes mm9 DNase-seq Blood B-Lymphocytes SRX188641,SRX14884...5,SRX191048,SRX148843,SRX037912,SRX148840,SRX148841,SRX148846,SRX148844,SRX148842 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/DNS.Bld.50.AllAg.B-Lymphocytes.bed ...

  19. File list: Pol.Bld.10.AllAg.B-Lymphocytes [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Bld.10.AllAg.B-Lymphocytes hg19 RNA polymerase Blood B-Lymphocytes SRX170357 ht...tp://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.Bld.10.AllAg.B-Lymphocytes.bed ...

  20. File list: ALL.Bld.05.AllAg.B-Lymphocytes [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Bld.05.AllAg.B-Lymphocytes mm9 All antigens Blood B-Lymphocytes SRX1046547,SRX2...X155015,SRX1091122,SRX021888,SRX021886,SRX317618,SRX148805 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Bld.05.AllAg.B-Lymphocytes.bed ...

  1. File list: His.Bld.20.AllAg.B-Lymphocytes [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Bld.20.AllAg.B-Lymphocytes hg19 Histone Blood B-Lymphocytes SRX110938,SRX271850...9,SRX091996,SRX722334 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/His.Bld.20.AllAg.B-Lymphocytes.bed ...

  2. File list: InP.Bld.10.AllAg.B-Lymphocytes [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Bld.10.AllAg.B-Lymphocytes mm9 Input control Blood B-Lymphocytes SRX1287947,SRX...5015 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Bld.10.AllAg.B-Lymphocytes.bed ...

  3. File list: Oth.Bld.20.AllAg.B-Lymphocytes [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Bld.20.AllAg.B-Lymphocytes mm9 TFs and others Blood B-Lymphocytes SRX1287946,SR...X1091123,SRX148805,SRX217128,SRX217126 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Bld.20.AllAg.B-Lymphocytes.bed ...

  4. File list: Pol.Bld.50.AllAg.B-Lymphocytes [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Bld.50.AllAg.B-Lymphocytes hg19 RNA polymerase Blood B-Lymphocytes SRX170357 ht...tp://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.Bld.50.AllAg.B-Lymphocytes.bed ...

  5. File list: NoD.Bld.10.AllAg.B-Lymphocytes [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available NoD.Bld.10.AllAg.B-Lymphocytes mm9 No description Blood B-Lymphocytes SRX338807,SRX...RX347812,SRX347813,SRX347811 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/NoD.Bld.10.AllAg.B-Lymphocytes.bed ...

  6. Glucose-dependent de Novo Lipogenesis in B Lymphocytes

    Science.gov (United States)

    Dufort, Fay J.; Gumina, Maria R.; Ta, Nathan L.; Tao, Yongzhen; Heyse, Shannon A.; Scott, David A.; Richardson, Adam D.; Seyfried, Thomas N.; Chiles, Thomas C.

    2014-01-01

    Bacterially derived lipopolysaccharide (LPS) stimulates naive B lymphocytes to differentiate into immunoglobulin (Ig)-secreting plasma cells. Differentiation of B lymphocytes is characterized by a proliferative phase followed by expansion of the intracellular membrane secretory network to support Ig production. A key question in lymphocyte biology is how naive B cells reprogram metabolism to support de novo lipogenesis necessary for proliferation and expansion of the endomembrane network in response to LPS. We report that extracellularly acquired glucose is metabolized, in part, to support de novo lipogenesis in response to LPS stimulation of splenic B lymphocytes. LPS stimulation leads to increased levels of endogenous ATP-citrate lyase (ACLY), and this is accompanied by increased ACLY enzymatic activity. ACLY produces cytosolic acetyl-CoA from mitochondrially derived citrate. Inhibition of ACLY activity in LPS-stimulated B cells with the selective inhibitor 2-hydroxy-N-arylbenzenesulfonamide (compound-9; C-9) blocks glucose incorporation into de novo lipid biosynthesis, including cholesterol, free fatty acids, and neutral and acidic phospholipids. Moreover, inhibition of ACLY activity in splenic B cells results in inhibition of proliferation and defective endomembrane expansion and reduced expression of CD138 and Blimp-1, markers for plasma-like B cell differentiation. ACLY activity is also required for LPS-induced IgM production in CH12 B lymphoma cells. These data demonstrate that ACLY mediates glucose-dependent de novo lipogenesis in response to LPS signaling and identify a role for ACLY in several phenotypic changes that define plasma cell differentiation. PMID:24469453

  7. 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

  8. FcgammaRIIb expression on human germinal center B lymphocytes.

    Science.gov (United States)

    Macardle, Peter J; Mardell, Carolyn; Bailey, Sheree; Wheatland, Loretta; Ho, Alice; Jessup, Claire; Roberton, Donal M; Zola, Heddy

    2002-12-01

    IgG antibody can specifically suppress the antibody response to antigen. This has been explained by the hypothesis that signaling through the B cell antigen receptor is negatively modulated by the co-ligation of immunoglobulin with the receptor for IgG, FcgammaRIIb. We hypothesized that inhibitory signaling through FcgammaRIIb would be counter-productive in germinal center cells undergoing selection by affinity maturation, since these cells are thought to receive a survival/proliferative signal by interacting with antigen displayed on follicular dendritic cells. We have identified and characterized a population of B lymphocytes with low/negative FcgammaRIIb expression that are present in human tonsil. Phenotypically these cells correspond to germinal center B cells and comprise both centroblast and centrocyte populations. In examining expression at the molecular level we determined that these B cells do not express detectable mRNA for FcgammaRIIb. We examined several culture conditions to induce expression of FcgammaRIIb on germinal center cells but could not determine conditions that altered expression. We then examined the functional consequence of cross-linking membrane immunoglobulin and the receptor for IgG on human B lymphocytes. Our results cast some doubt on the value of anti-IgG as a model for antigen-antibody complexes in studying human B cell regulation.

  9. T- and B-lymphocyte chimerism in the marmoset

    Energy Technology Data Exchange (ETDEWEB)

    Niblack, G.D.; Kateley, J.R.; Gengozian, N.

    1977-01-01

    Marmosets are natural blood chimeras, this condition resulting from the high frequency of fraternal twinning and the consistent development of placental vascular anastomoses between the two embryos. Identification of chimerism by sex-chromosome analysis of cultured blood lymphocytes provided a means of determining the proportion of chimerism among T and B lymphocytes. Peripheral blood lymphocytes were enriched for T or B cells by filtration through a nylon column (yields >95% T-cells) or inactivation of T lymphocytes by treatment with a goat anti-marmoset thymocyte antiserum in the presence of complement (yields >95% B cells). Mitogenic stimulation of these separated, enriched cell populations yielded metaphase plates which could be scored for percentage male and female cells. Tests on five different blood chimeras showed the T- and B-lymphocyte chimerism to be the same. Stimulation of blood lymphocytes with cells from another species of marmoset in a mixed lymphocyte culture test revealed the chimeric T-cell response (i.e., host and co-twin cells) to be similar to that obtained with a mitogenic lectin. The demonstration of equivalent T- and B-cell chimerism in these animals suggests derivation of these cells from a common stem cell pool and the response of both T-cell populations to an antigenic stimulus in proportions similar to their percentage chimerism suggests complete immunologic tolerance exists in this species for co-twin histocompatibility antigens.

  10. 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.

  11. ROLE OF B LYMPHOCYTE AND ITS SUBPOPULATIONS IN PATHOGENESIS OF IMMUNORELATED PANCYTOPENIA

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective To measure the quantities and apoptosis-related protein levels of B lymphocyte in the patients with immunorelated pancytopenia (IRP) and explore the action of B lymphocyte in the pathogenic mechanism of IRP.Methods Quantities of whole B lymphocytes and CD5 + B lymphocytes as well as the expressions of Fas and Bcl-2in B lymphocytes in 35 patients with untreated IRP, 15 IRP patients in complete remission (CR), and 10 normal controls were assayed by flow cytometry.Results The percentages of B lymphocyte and CD5 + B lymphocyte were significantly higher in untreated IRP patients than in CR IRP patients and normal controls ( P < 0. 05 ), and there was no significant difference between the latter two groups (P > 0. 05). There was no significant difference of Fas expression in B lymphocyte among three groups (P >0. 05). The expression of Bcl-2 in B lymphocyte was significantly higher in untreated patients than in CR patients or normal controls (P <0. 01 ), and significantly higher in CR patients than in normal controls (P <0. 01 ). The apoptosisrelated index was significantly lower in untreated patients than in CR patients or normal controls ( P < 0. 05 ), and significantly lower in CR patients than in normal controls ( P < 0. 05 ). The percentage of B lymphocyte was positively correlated with post-treated response time ( r = 0. 53, P < 0. 01 ).Conclusion The production of auto-antibodies in IRP patients probably has some relationship with the abnormal quantities of B lymphocyte and its subpopulations as well as with the inhibition of B lymphocyte apoptosis.

  12. Activation-induced cell death in B lymphocytes

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Upon encountering the antigen (Ag), the immune system can either develop a specific immune response or enter a specific state of unresponsiveness, tolerance. The response of B cells to their specific Ag can be activation and proliferation, leading to the immune response, or anergy and activation-induced cell death (AICD), leading to tolerance. AICD in B lymphocytes is a highly regulated event initiated by crosslinking of the B cell receptor (BCR). BCR engagement initiates several signaling events such as activation of PLCγ, Ras, and PI3K, which generally speaking, lead to survival However, in the absence of survival signals (CD40 or IL-4R engagement), BCR crosslinking can also promote apoptotic signal transduction pathways such as activation of effector caspases, expression of pro-apoptotic genes, and inhibition of pro-survival genes. The complex interplay between survival and death signals determines the B cell fate and, consequently, the immune response.

  13. 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 J

    2007-01-01

    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...

  14. 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...

  15. Expression of activated molecules on CD5(+)B lymphocytes in autoimmune hemolytic anemia.

    Science.gov (United States)

    Zhu, Hongli; Xu, Wenyan; Liu, Hong; Wang, Huaquan; Fu, Rong; Wu, Yuhong; Qu, Wen; Wang, Guojin; Guan, Jing; Song, Jia; Xing, Limin; Shao, Zonghong

    2016-05-01

    To investigate the expression of activation molecules on CD5(+)B lymphocytes in peripheral blood of autoimmune hemolytic anemia (AIHA)/Evans patients. The expression of CD80, CD86, and CD69 on CD5(+)B lymphocytes was detected using flow cytometry in 30 AIHA/Evans patients, 18 normal controls (NC) and nine chronic lymphocytic leukemia (CLL) patients. CD80 on CD5(+)B lymphocytes in untreated patients was higher than that in remission patients (P 0.05), but lower than those of CD5(-)B lymphocytes in remission patients and NC (P 0.05). CD80 and CD86 on CD5(+)B lymphocytes was negatively correlated with hemoglobin (HB), C3, C4 (P < 0.05) and positively correlated with reticulocyte (Ret) (P < 0.05). CD69 on CD5(+) and CD5(-)B lymphocytes of CLL was higher than those of AIHA/Evans patients and NC (P < 0.05). The active molecules on CD5(+)B lymphocytes in peripheral blood of AIHA/Evans patients differ from those on CD5(-) and clonal CD5(+)B lymphocytes.

  16. Phenotypic and functional characteristics of human newborns' B lymphocytes.

    Science.gov (United States)

    Durandy, A; Thuillier, L; Forveille, M; Fischer, A

    1990-01-01

    It has been demonstrated two major facts concerning human newborns' B lymphocytes: 1) they differentiate poorly into Ig-producing cells and 2) they express CD5 and CD1c membrane proteins. We have further analyzed human newborns' B cell characteristics and found that approximately half of them express activation Ag, i.e., 4F2 and IL-2R, both associated in significant proportions with CD23 and Bac-1. These membrane Ag were found both on CD5(+) and CD5(-) B cells. Newborns' B cells do not exhibit other activation markers because they express surface IgD, and because their size, RNA, and DNA contents do not differ from those of adults' B cells, indicating that they are in the G0/G1 cell cycle phase. Newborns' B cell proliferation can be induced by rIL-2, rIL-4, low m.w. B cell growth factor, and by Staphylococcus aureus protein A. It is presently difficult to build a hypothesis accounting for all the specific findings made on newborns' B cells. It is not known for instance whether CD5(+) and (-) B cells belong to distinct subsets as suggested by the fluorescence intensity curve obtained with an anti-CD5 antibody or to distinct stages in a unique pattern of B cell maturation during fetal and newborn life. This may indicate that partially activated B cells actually produce natural polyspecific autoantibodies of the IgM isotype found in newborns' human serum.

  17. Effect of in vitro x-irradiation on human peripheral blood T and B lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    Prusek, W. (Szpital Wojewodzki, Wroclaw (Poland)); Astaldi, G. (The Blood Research Foundation Centre, Tortona (Italy))

    1979-01-01

    The effect of in vitro irradiation with increasing in logarythmic progress X-ray doses on lymphocyte viability and on T and B lymphocyte populations was studied in normal adults, patients with myasthenia gravis and in patients undergoing long-term steroid therapy. Decrease in numbers of lymphocytes carrying T or B lymphocyte surface markers was higher than the viable cell loss. The decrease showed no linear correlation with X-ray doses applied, which might reflect the existence of radioresistant T and B lymphocytes. A higher so-called early radiosensitivity of B lymphocytes was demonstrated. In patients with myasthenia gravis early radioresistance of T lymphocytes was detected. In patients undergoing long-term steroid therapy, an increase in numbers of cells lacking markers of any of lymphocyte populations was found in parallel with a decrease in T lymphocyte number which, in these patients, showed a higher radiosensitivity.

  18. 2-Methoxyestradiol induce the conversion of human peripheral blood memory B lymphocytes into plasma cells.

    Science.gov (United States)

    Cayer, Marie-Pierre; Drouin, Mathieu; Proulx, Maryse; Jung, Daniel

    2010-04-15

    2-Methoxyestradiol (2ME), an end-metabolite of 17beta-estradiol, is an antiproliferative agent that is currently being tested in clinical trials for cancer treatment. We hereby report that sub-cytotoxic concentrations of 2ME influence the in vitro proliferation of human peripheral blood B lymphocytes. More surprisingly, we have observed that 2ME induces the conversion of CD138(-) B lymphocytes into CD138(+) cells of phenotype similar to immunoglobulin (Ig)-secreting plasma cells. Normal human B lymphocytes expressing CD138 increased in response to 2ME in a dose-dependent fashion, from 2% at baseline up to 31% in cells cultured in the presence of 0.75 microM 2ME. Moreover, most of the converted cells were also CD27(+) and secreted high levels of IgG (151 microg/10(6)cells/24h). IEF studies revealed that conversion occurred in a polyclonal manner. We then exploited this effect of 2ME to gain further insights into the molecular mechanisms that govern changes in transcription factors involved in plasma cells differentiation. Plasma cells generated by 2ME treatment of normal human B lymphocytes expressed elevated levels of IRF4 and reduced levels of Pax5 and Bcl-6. Similarly, levels of XBP-1 and Blimp-1 transcripts were increased. Our results suggest that the differentiation of peripheral blood B lymphocytes into plasma cells requires a similar modulation of transcription factors expression that for tonsil and bone marrow B lymphocytes.

  19. Platelet-Activating Factor Antagonists Decrease Follicular Dendritic-Cell Stimulation of Human B Lymphocytes

    Directory of Open Access Journals (Sweden)

    Halickman Isaac

    2005-06-01

    Full Text Available Abstract Both B-lymphoblastoid cell lines and tonsillar B lymphocytes express receptors for platelet-activating factor (PAF. In lymph node germinal centres, B lymphocytes interact with follicular dendritic cells (FDCs, which present antigen-containing immune complexes to B lymphocytes. FDCs have phenotypic features that are similar to those of stromal cells and monocytes and may therefore be a source of lipid mediators. In this study, we evaluated the effects of the PAF antagonist WEB 2170 on the activation of tonsillar B lymphocytes by FDCs. FDCs were isolated from tonsils by Bovine Serum Albumin (BSA gradient centrifugation. After being cultured for 6 to 10 days, they were incubated with freshly isolated B cells in the presence or absence of the specific PAF receptor antagonist WEB 2170. B-lymphocyte proliferation was assessed by [3H]-thymidine incorporation, and immunoglobulin (Ig G and IgM secretion was assessed by enzyme-linked immunosorbent assay (ELISA. WEB 2170 (10-6 to 10-8 M inhibited [3H]-thymidine incorporation by up to 35% ± 3%. Moreover, the secretion of IgG and IgM was inhibited by up to 50% by WEB 2170 concentrations ranging from 10-6 to 10-8 M. There was no evidence of toxicity by trypan blue staining, and the addition of WEB 2170 to B cells in the absence of FDCs did not inhibit the spontaneous production of IgG or IgM. The effect of the PAF antagonist is primarily on B lymphocytes, as reverse transcription polymerase chain reaction detected little PAF receptor messenger ribonucleic acid (mRNA from FDCs. These data suggest that endogenous production of PAF may be important in the interaction of B lymphocytes with FDCs.

  20. Classical scrapie prions in ovine blood are associated with B lymphocytes and platelet-rich plasma

    Directory of Open Access Journals (Sweden)

    Dassanayake Rohana P

    2011-11-01

    Full Text Available Abstract Background Classical scrapie is a naturally occurring transmissible spongiform encephalopathy of sheep and goats characterized by cellular accumulation of abnormal isoforms of prion protein (PrPSc in the central nervous system and the follicles of peripheral lymphoid tissues. Previous studies have shown that the whole blood and buffy coat blood fraction of scrapie infected sheep harbor prion infectivity. Although PrPSc has been detected in peripheral blood mononuclear cells (PBMCs, plasma, and more recently within a subpopulation of B lymphocytes, the infectivity status of these cells and plasma in sheep remains unknown. Therefore, the objective of this study was to determine whether circulating PBMCs, B lymphocytes and platelets from classical scrapie infected sheep harbor prion infectivity using a sheep bioassay. Results Serial rectal mucosal biopsy and immunohistochemistry were used to detect preclinical infection in lambs transfused with whole blood or blood cell fractions from preclinical or clinical scrapie infected sheep. PrPSc immunolabeling was detected in antemortem rectal and postmortem lymphoid tissues from recipient lambs receiving PBMCs (15/15, CD72+ B lymphocytes (3/3, CD21+ B lymphocytes (3/3 or platelet-rich plasma (2/3 fractions. As expected, whole blood (11/13 and buffy coat (5/5 recipients showed positive PrPSc labeling in lymphoid follicles. However, at 549 days post-transfusion, PrPSc was not detected in rectal or other lymphoid tissues in three sheep receiving platelet-poor plasma fraction. Conclusions Prion infectivity was detected in circulating PBMCs, CD72+ pan B lymphocytes, the CD21+ subpopulation of B lymphocytes and platelet-rich plasma of classical scrapie infected sheep using a sheep bioassay. Combining platelets with B lymphocytes might enhance PrPSc detection levels in blood samples.

  1. 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.

  2. 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

  3. 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.

  4. Is there a difference between T- and B-lymphocyte morphology?

    NARCIS (Netherlands)

    Strokotov, D.I.; Yurkin, M.A.; Gilev, K.V.; van Bockstaele, D.R.; Hoekstra, A.G.; Rubtsov, N.B.; Maltsev, V.P.

    2009-01-01

    We characterize T- and B-lymphocytes from several donors, determining cell diameter, ratio of nucleus to cell diameter, and refractive index of the nucleus and cytoplasm for each individual cell. We measure light-scattering profiles with a scanning flow cytometer and invert the signals using a coate

  5. 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.

  6. Resveratrol Alters Proliferative Responses and Apoptosis in Human Activated B Lymphocytes In Vitro

    Science.gov (United States)

    We hypothesized that resveratrol, a polyphenol found in grapes, peanuts, and berries would modulate B lymphocyte proliferation, immunoglobulin synthesis, and apoptosis after activation with T-cell dependent pokeweed mitogen. Peripheral blood mononuclear cells (PBMCs) were isolated from the blood of ...

  7. Tc-99m-labeled Rituximab for Imaging B Lymphocyte Infiltration in Inflammatory Autoimmune Disease Patients

    NARCIS (Netherlands)

    Malviya, G.; Anzola, K. L.; Podesta, E.; Lagana, B.; Del Mastro, C.; Dierckx, R. A.; Scopinaro, F.; Signore, A.

    2012-01-01

    The rationale of the present study was to radiolabel rituximab with 99m-technetium and to image B lymphocytes infiltration in the affected tissues of patients with chronic inflammatory autoimmune diseases, in particular, the candidates to be treated with unlabelled rituximab, in order to provide a r

  8. TRPML cation channels regulate the specialized lysosomal compartment of vertebrate B-lymphocytes.

    Science.gov (United States)

    Song, Yumei; Dayalu, Rashmi; Matthews, Sharon A; Scharenberg, Andrew M

    2006-12-01

    B-lymphocytes possess a specialized lysosomal compartment, the regulated transformation of which has been implicated in B-cell antigen presentation. Members of the mucolipin (TRPML) family of cation channels have been implicated in regulated vesicular transport in several tissues, but a role for TRPML function in lymphocyte vesicular transport physiology has not been previously described. To address the role of TRPML proteins in lymphocyte vesicular transport, we analyzed the lysosomal compartment in cultured B-lymphocytes engineered to lack TRPML1 or after expression of N- or C-terminal GFP fusion proteins of TRPML1 or TRPML2. Consistent with previous analyses of lymphocytes derived from human patients with mutations in TRPML1, we were not able to detect abnormalities in the lysosomes of TRPML1-deficient DT40 B-lymphocytes. However, while N-terminal GFP fusions of TRPML2 localized to normal appearing lysosomes, C-terminal GFP fusions of either TRPML1 or TRPML2 acted to antagonize endogenous TRPML function, localizing to large vesicular structures, the histological properties of which were indistinguishable from the enlarged lysosomes observed in affected tissues of TRPML1-deficient humans. Endocytosed B-cell receptors were delivered to these enlarged lysosomes, demonstrating that a TRPML-dependent process is required for normal regulation of the specialized lysosome compartment of vertebrate B-lymphocytes.

  9. Stress, Cortisol, and B-Lymphocytes: A Novel Approach to Understanding Academic Stress and Immune Function

    Science.gov (United States)

    McGregor, Bonnie A; Murphy, Karly Mary; 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. PMID:26644211

  10. Expression of molecules involved in B lymphocyte survival and differentiation by synovial fibroblasts.

    Science.gov (United States)

    Edwards, J C; Leigh, R D; Cambridge, G

    1997-06-01

    The synovitis of rheumatoid arthritis (RA) is one of few pathological lesions in which B lymphocyte accumulation progresses to the extent of germinal centre formation. The present study was designed to assess the ability of synovial fibroblasts to express molecules implicated in B lymphocyte survival and differentiation, both in vivo, and in response to cytokines in vitro. Normal and diseased synovia were examined by indirect immunofluorescence. In all tissues synovial intimal fibroblasts showed co-expression of vascular cell adhesion molecule-1 (VCAM-1) and complement decay-accelerating factor (DAF) comparable to that of follicular dendritic cells (FDC), but not complement receptor 2 (CR2). In rheumatoid synovia, subintimal cells showed variable expression of VCAM-1 and DAF, with bright co-expression of VCAM-1, DAF and CR2 in lymphoid follicle centres. B lymphocytes, some of which were proliferating cell nuclear antigen-positive, were present in contact with subintimal cells expressing VCAM-1 with or without DAF or CR2. B lymphocytes were rarely present in the intimal layer, and, where present, showed fragmentation. In vitro, synovial fibroblasts exposed to tumour necrosis factor-alpha (TNF-alpha) in combination with interferon-gamma (IFN-gamma) showed enhanced expression of VCAM-1, in comparison with fibroblasts from skin and lung and, unlike skin and lung fibroblasts, also expressed DAF and CR2. These findings support the hypothesis that synovial targeting in RA involves an enhanced ability of synovial fibroblasts to support B lymphocyte survival. This appears to be dependent, not on the constitutive expression of VCAM-1 and DAF on intimal cells, but on the increased ability of subintimal cells to respond to proinflammatory cytokines, perhaps critically in the expression of VCAM-1.

  11. Is there a difference between T- and B-lymphocyte morphology?

    Science.gov (United States)

    Strokotov, Dmitry I; Yurkin, Maxim A; Gilev, Konstantin V; van Bockstaele, Dirk R; Hoekstra, Alfons G; Rubtsov, Nikolay B; Maltsev, Valeri P

    2009-01-01

    We characterize T- and B-lymphocytes from several donors, determining cell diameter, ratio of nucleus to cell diameter, and refractive index of the nucleus and cytoplasm for each individual cell. We measure light-scattering profiles with a scanning flow cytometer and invert the signals using a coated sphere as an optical model of the cell and by relying on a global optimization technique. The main difference in morphology of T- and B-lymphocytes is found to be the larger mean diameters of the latter. However, the difference is smaller than the natural biological variability of a single cell. We propose nuclear inhomogeneity as a possible reason for the deviation of measured light-scattering profiles from real lymphocytes from those obtained from the coated sphere model.

  12. An experimental system for determining the influence of microgravity on B lymphocyte activation and cell fusion

    Science.gov (United States)

    Sammons, D. W.; Zimmermann, U.; Klinman, N. R.; Gessner, P.; Humphreys, R. C.; Emmons, S. P.; Neil, G. A.

    The influence of microgravity on lymphocyte activation is central to the understanding of immunological function in space. Moreover, the adaptation of groundbased technologies to microgravity conditions presents opportunities for biotechnological applications including high efficiency production of antibody forming hybridomas. Because the emerging technology of microgravity hybridoma generation is dependent upon activation and cultivation of B lymphocytes during flight, we have adapted mitogen-driven B lymphocyte stimulation and culture that allows for the in vitro generation of large numbers of antibody forming cells suitable for cell fusion over a period of 1-2 weeks. We believe that this activation and cultivation system can be flown on near-term space flights to test fundamental hypotheses about mammalian cell activation, cell fusion, metabolism, secretion, growth, and bio-separation.

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

    Science.gov (United States)

    2014-08-01

    Aim 2. To identify novel TRAF3- interacting proteins in mitochondria of B lymphocytes 1 PI: Ping Xie, PhD Considering that TRAF3 does not...mitochondrial proteins. To test this, we propose to identify novel mitochondrial TRAF3- interacting proteins using biochemical affinity purification...mitochondrial TRAF3- interacting proteins : 100% completed. 2c. Mass spectrometry-based sequencing of purified proteins: 100% completed. 2d. Proteomic

  14. Stimulation of rat B-lymphocyte proliferation by corticotropin-releasing factor.

    Science.gov (United States)

    McGillis, J P; Park, A; Rubin-Fletter, P; Turck, C; Dallman, M F; Payan, D G

    1989-07-01

    The mitogenic effect of corticotropin-releasing factor (CRF) on rat lymphocytes was investigated. When rat splenocytes were cultured for 48 hr with CFR, a dose-dependent increase in incorporation of 3H-thymidine (3H-Tdr) was observed, with a maximal response at 10 nM CRF. Comparison of the proliferative effect of CRF on enriched populations of B lymphocytes, T lymphocytes, or macrophages revealed that only B lymphocytes responded following treatment with CRF. When lymphocytes derived from different lymphoid tissues were compared, CRF had a greater proliferative effect on lymphocytes derived from gut-associated lymphoid tissue (mesenteric lymph nodes and Peyer's patches) than on lymphocytes from spleen or inguinal lymph nodes; CRF had no effect on thymocytes. Synthetic fragments of CRF were used to determine which portions of the peptide are recognized by lymphocytes. The C-terminal fragments alpha-helical CRF9-41 and CRF21-41 were as potent as native CRF in stimulating B-lymphocyte proliferation, whereas CRF1-20 did not stimulate proliferation. The activity of these peptides suggests that CRF stimulates lymphocyte proliferation by cellular recognition of structural determinants in the C-terminal one-half of the peptide.

  15. NFAT1 transcription factor regulates cell cycle progression and cyclin E expression in B lymphocytes.

    Science.gov (United States)

    Teixeira, Leonardo K; Carrossini, Nina; Sécca, Cristiane; Kroll, José E; DaCunha, Déborah C; Faget, Douglas V; Carvalho, Lilian D S; de Souza, Sandro J; Viola, João P B

    2016-09-01

    The NFAT family of transcription factors has been primarily related to T cell development, activation, and differentiation. Further studies have shown that these ubiquitous proteins are observed in many cell types inside and outside the immune system, and are involved in several biological processes, including tumor growth, angiogenesis, and invasiveness. However, the specific role of the NFAT1 family member in naive B cell proliferation remains elusive. Here, we demonstrate that NFAT1 transcription factor controls Cyclin E expression, cell proliferation, and tumor growth in vivo. Specifically, we show that inducible expression of NFAT1 inhibits cell cycle progression, reduces colony formation, and controls tumor growth in nude mice. We also demonstrate that NFAT1-deficient naive B lymphocytes show a hyperproliferative phenotype and high levels of Cyclin E1 and E2 upon BCR stimulation when compared to wild-type B lymphocytes. NFAT1 transcription factor directly regulates Cyclin E expression in B cells, inhibiting the G1/S cell cycle phase transition. Bioinformatics analysis indicates that low levels of NFAT1 correlate with high expression of Cyclin E1 in different human cancers, including Diffuse Large B-cell Lymphomas (DLBCL). Together, our results demonstrate a repressor role for NFAT1 in cell cycle progression and Cyclin E expression in B lymphocytes, and suggest a potential function for NFAT1 protein in B cell malignancies.

  16. Lipid raft-dependent plasma membrane repair interferes with the activation of B lymphocytes.

    Science.gov (United States)

    Miller, Heather; Castro-Gomes, Thiago; Corrotte, Matthias; Tam, Christina; Maugel, Timothy K; Andrews, Norma W; Song, Wenxia

    2015-12-21

    Cells rapidly repair plasma membrane (PM) damage by a process requiring Ca(2+)-dependent lysosome exocytosis. Acid sphingomyelinase (ASM) released from lysosomes induces endocytosis of injured membrane through caveolae, membrane invaginations from lipid rafts. How B lymphocytes, lacking any known form of caveolin, repair membrane injury is unknown. Here we show that B lymphocytes repair PM wounds in a Ca(2+)-dependent manner. Wounding induces lysosome exocytosis and endocytosis of dextran and the raft-binding cholera toxin subunit B (CTB). Resealing is reduced by ASM inhibitors and ASM deficiency and enhanced or restored by extracellular exposure to sphingomyelinase. B cell activation via B cell receptors (BCRs), a process requiring lipid rafts, interferes with PM repair. Conversely, wounding inhibits BCR signaling and internalization by disrupting BCR-lipid raft coclustering and by inducing the endocytosis of raft-bound CTB separately from BCR into tubular invaginations. Thus, PM repair and B cell activation interfere with one another because of competition for lipid rafts, revealing how frequent membrane injury and repair can impair B lymphocyte-mediated immune responses.

  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-lym......-lymphocyte deficiency did not interfere with the development of periodontal disease in this model, whereas a temporary and moderate reduction in B-lymphocyte numbers seemed to predispose for aggravation of periodontal bone loss.......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...... 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. B-lymphocyte reconstitution after repeated rituximab treatment in a child with steroid-dependent autoimmune hemolytic anemia

    Directory of Open Access Journals (Sweden)

    Esther de Vries

    2011-09-01

    Full Text Available We report the detailed long-term reconstitution of B-lymphocyte subpopulations, immunoglobulins, and specific antibody production after two courses of rituximab in a young, previously healthy girl with steroid-dependent autoimmune hemolytic anemia. B-lymphocyte subpopulations were surprisingly normal directly after reconstitution. However, there was a slower reconstitution after the second rituximab course, especially of non-switched and switched memory B-lymphocytes, and a temporary decline in IgM below age-matched reference values.

  19. 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

    2001-01-01

    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

  20. 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

  1. The glycoprotein isolated from vesicular stomatitis virus is mitogenic for mouse B lymphocytes

    OpenAIRE

    1981-01-01

    The glycoprotein (G protein) of VSV was purified from the intact virion by Triton X-100 extraction. The isolated G protein has been shown to be a T cell-independent, B lymphocyte mitogen and polyclonal activator. Neither G protein nor the intact virion are stimulatory for murine T lymphocytes. The greater the density of G protein in lipid vesicles or the degree of aggregation of isolated G protein, the more highly stimulatory it is for murine splenocytes. As G protein is spread out in artific...

  2. Change of T, B lymphocyte subsets and Th1/Th2 indexes of patients with recurrent spontaneous abortion

    Institute of Scientific and Technical Information of China (English)

    Shi-Hua Zhou

    2016-01-01

    Objective:To analyze and investigate the change state of T, B lymphocyte subsets and Th1/Th2 indexes of patients with recurrent spontaneous abortion. Methods: A total of 92 patients with recurrent spontaneous abortion in our hospital from June 2013 to July 2015 were selected as the observation group and 92 women with health delivery history at the same time were selected as the control group,then the peripheral blood T, B lymphocyte subsets and Th1/Th2 indexes of two groups were detected and compared and the peripheral blood T, B lymphocyte subsets and Th1/Th2 indexes of patients with different gestational age at abortion and abortion times were compared too. Results:The peripheral blood T, B lymphocyte subsets and Th1/Th2 indexes of observation group and control group all had obvious differences,and those blood indexes levels' differences of patients with different gestational age at abortion and abortion times were obvious too, all P<0.05 and the differences were significant. Conclusions: The T, B lymphocyte subsets and Th1/Th2 indexes of patients with recurrent spontaneous abortion show abnormal state and the differences of detection results of patients with different gestational age at abortion and abortion times are relatively obvious,so those indexes should be monitored and improved intentinonally.

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

    Directory of Open Access Journals (Sweden)

    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

  4. Effect of cholinomimetics and adrenomimetics on proliferation of mouse B lymphocytes during primary immune response to protein antigen

    Energy Technology Data Exchange (ETDEWEB)

    Ado, A.D.; Dontsov, V.I.; Gol' dshtein, M.M.

    1985-12-01

    The aim of this investigation was to study the effect of neurotransmitters on proliferation of B lymphocytes induced by specific antigen. Experiments were carried out on female mice. To estimate proliferative activity, lymphocytes enriched with B cells were incubated in medium 199 for 2 h at 37 degrees C in a dose of 2.10/sup 6/-5.10/sup 6/ cells with 2 microCi of /sup 3/H-(methyl)-thymidine. The effect of acetylcholine on incorporation of /sup 3/H-thymidine into B lymphocytes of mice immunized with different doses of antigen during culture is shown. Discordance of effects of adrenalin and acetylcholine on incorporation of /sup 3/H-thymidine into B lymphocytes of mice immunized with different doses of ovalbumin is also shown.

  5. Deletion of Cmu genes in mouse B lymphocytes upon stimulation with LPS.

    Science.gov (United States)

    Radbruch, A; Sablitzky, F

    1983-01-01

    Mouse B lymphocytes can be activated polyclonally by bacterial lipopolysaccharide (LPS) to differentiate into plasmablasts. Within several days many cells perform immunoglobulin (Ig) class switching in vitro. We have purified LPS blasts expressing IgM or only IgG3 on the cell surface and analysed the DNA of these cells by Southern hybridisation blotting to detect rearrangement or deletion of CH genes. Quantitative evaluation of the Southern blots suggests that populations of surface IgG3+ (sIgG3+) cells from 6-day and sIgM+ cells from 8-day-old cultures contain only about half as many Cmu genes as spleen cells. Cmu deletion is nearly complete in populations of sIgG3+ cells from 9-day-old cultures. Therefore, upon stimulation with LPS, within a few days Cmu is deleted in most sIgG3+ cells from both chromosomes.

  6. Generation and characterization of human B lymphocyte stimulator blocking monoclonal antibody.

    Science.gov (United States)

    Zhuang, Weiliang; Zhang, Jianjun; Pei, Lili; Fang, Shuping; Liu, Honghao; Wang, Ruixue; Su, Yunpeng

    2016-09-01

    The cytokine, B lymphocyte stimulator (Blys) is essential for activation and proliferation of B cells and is involved in the pathogenesis of B-cell mediated autoimmune diseases. Based on its essential activity, Blys may be a potential therapeutic target for human autoimmune diseases. In this article, we have described the development of a novel humanized anti-Blys antibody, NMB04, that binds with high affinity and specificity to both soluble and membrane bound Blys. This monoclonal antibody has the potential to block Blys binding to all its three receptors, TACI, BCMA and BR-3. Further in vivo studies revealed that NMB04 possessed more potent inhibitory activity against human Blys as compared to an existing antibody, Belimumab. Therefore, NMB04 may have potential as a therapeutic candidate targeting autoimmune diseases.

  7. Early B lymphocyte development: Similarities and differences in human and mouse

    Institute of Scientific and Technical Information of China (English)

    Michiko; Ichii; Kenji; Oritani; Yuzuru; Kanakura

    2014-01-01

    B lymphocytes differentiate from hematopoietic stem cells through a series of distinct stages. Early B cell development proceeds in bone marrow until immature B cells migrate out to secondary lymphoid tissues, such as a spleen and lymph nodes, after completion of immunoglobulin heavy and light chain rearrangement. Although the information about the regulation by numerous factors, including signaling molecules, transcription factors, epigenetic changes and the microenvironment, could provide the clinical application, our knowledge on human B lymphopoiesis is limited. However, with great methodological advances, significant progress for understanding B lymphopoiesis both in human and mouse has been made. In this review, we summarize the experimental models for studies about human adult B lymphopoiesis, and the role of microenvironment and signaling molecules, such as cytokines, transforming growth factor-β superfamily, Wnt family and Notch family, with point-by-point comparison between human and mouse.

  8. Functional capabilities of marmoset T and B lymphocytes in primary in vitro antibody formation

    Energy Technology Data Exchange (ETDEWEB)

    Nickerson, D.A.; Gengozian, N.

    1981-01-15

    In vitro tests of T- and B-lymphocyte function of two marmoset species, Saguinus fuscicollis and Saguinus oedipus, were examined to explore the lower immune response profile previously reported for S. o. oedipus. Experiments with trinitrophenyl-lipopolysaccharide (TNP-LPS) revealed peripheral blood leukocytes (PBL) from both species capable of antibody formation. This response was both T cell and monocyte independent; indeed, removal of T cells led to an enhanced response, indicating a regulatory role for this cell in each species. Studies with the nonmitogenic form of TNP-LPS, trinitrophenyl-base-hydrolyzed-lipopolysaccharide, revealed that plaque-forming cells could be obtained from S. fuscicollis PBL while S. o. oedipus PBL were unresponsive. This report also demonstrates that hemopoietic chimerism, a feature common to all marmosets, has a negative influence on antibody-forming capabilities.

  9. Effect of insulin and glucose on adenosine metabolizing enzymes in human B lymphocytes.

    Science.gov (United States)

    Kocbuch, Katarzyna; Sakowicz-Burkiewicz, Monika; Grden, Marzena; Szutowicz, Andrzej; Pawelczyk, Tadeusz

    2009-01-01

    In diabetes several aspects of immunity are altered, including the immunomodulatory action of adenosine. Our study was undertaken to investigate the effect of different glucose and insulin concentrations on activities of adenosine metabolizing enzymes in human B lymphocytes line SKW 6.4. The activity of adenosine deaminase in the cytosolic fraction was very low and was not affected by different glucose concentration, but in the membrane fraction of cells cultured with 25 mM glucose it was decreased by about 35% comparing to the activity in cells maintained in 5 mM glucose, irrespective of insulin concentration. The activities of 5'-nucleotidase (5'-NT) and ecto-5'-NT in SKW 6.4 cells depended on insulin concentration, but not on glucose. Cells cultured with 10(-8) M insulin displayed an about 60% lower activity of cytosolic 5'-NT comparing to cells maintained at 10(-11) M insulin. The activity of ecto-5'-NT was decreased by about 70% in cells cultured with 10(-8) M insulin comparing to cells grown in 10(-11) M insulin. Neither insulin nor glucose had an effect on adenosine kinase (AK) activity in SKW 6.4 cells or in human B cells isolated from peripheral blood. The extracellular level of adenosine and inosine during accelerated catabolism of cellular ATP depended on glucose, but not on insulin concentration. Concluding, our study demonstrates that glucose and insulin differentially affect the activities of adenosine metabolizing enzymes in human B lymphocytes, but changes in those activities do not correlate with the adenosine level in cell media during accelerated ATP catabolism, implying that nucleoside transport is the primary factor determining the extracellular level of adenosine.

  10. 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

  11. Circulating monocytes and B-lymphocytes in neovascular age-related macular degeneration

    Science.gov (United States)

    Hector, Sven Magnus; Sørensen, Torben Lykke

    2017-01-01

    Background Individuals with neovascular age-related macular degeneration (AMD) have altered number and distribution of retinal macrophages and show changes in circulating antibodies. We wanted to investigate the corresponding precursors, with subpopulations. We therefore measured monocyte and B-lymphocyte populations in individuals with neovascular AMD. Design This was an observational case–control study. Participants or samples A total of 31 individuals with neovascular AMD and 30 healthy age-matched controls were included. Methods Patients and controls were interviewed, and ophthalmological examination included visual acuity assessment using the Early Treatment Diabetic Retinopathy Study (ETDRS) chart, spectral domain optical coherence tomography (SD-OCT), slit-lamp examination and fundus photography. Moreover, venous blood was drawn and prepared for flow cytometry. Cells were gated and measured for surface markers. Main outcome measures Relative amounts of monocytes and B-lymphocytes with subsets, as well as selected surface markers, were measured. Results The two groups did not significantly differ in age, smoking history, body mass index, physical activity or C-reactive protein (CRP). Total monocytes (percentage of all leukocytes) were lower in the neovascular AMD group (median 5.5%) compared with the level in the control group (6.5%; P-value: 0.028). The percentage of intermediate monocytes positive for cluster of differentiation 11b (CD11b) was lower for AMD patients (99.4%) compared with 100% for the control group (P-value: 0.032). Conclusion We observed lower numbers of monocytes, which show a potentially impaired ability to migrate across the endothelial wall in patients with neovascular AMD. These subtle changes could potentially lead to an imbalance in the recruitment of macrophages into the retina during disease development. PMID:28176950

  12. Carbon nanotube-mediated delivery of nucleic acids does not result in non-specific activation of B lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    Cai Dong [Department of Biology, Boston College, Chestnut Hill, MA 02467 (United States); Doughty, Cheryl A [Department of Biology, Boston College, Chestnut Hill, MA 02467 (United States); Potocky, Terra B [Department of Biology, Boston College, Chestnut Hill, MA 02467 (United States); Dufort, Fay J [Department of Biology, Boston College, Chestnut Hill, MA 02467 (United States); Huang Zhongping [NanoLab, Incorporated, Newton, MA 02458 (United States); Blair, Derek [Department of Biology, Boston College, Chestnut Hill, MA 02467 (United States); Kempa, Krzysztof [Department of Physics, Boston College, Chestnut Hill, MA 02467 (United States); Ren, Z F [Department of Physics, Boston College, Chestnut Hill, MA 02467 (United States); Chiles, Thomas C [Department of Biology, Boston College, Chestnut Hill, MA 02467 (United States)

    2007-09-12

    The efficient delivery of genes and proteins into primary mammalian cells and tissues has represented a formidable challenge. Recent advances in the research of carbon nanotubes (CNTs) offer much promise for their use as delivery platforms into mammalian cells. Ideally, CNT-mediated applications should not result in cellular toxicity nor perturb cellular homeostasis (e.g., result in non-specific activation of primary cells). It is therefore critical to evaluate the impact of CNT exposure on the cellular metabolism, proliferation and survival of primary mammalian cells. We investigated the compatibility of a recently developed CNT-mediated delivery method, termed nanospearing, with primary ex vivo cultures of B lymphocytes. Several parameters were evaluated to assess the impact of CNTs on naive B lymphocytes, including cell survival, activation, proliferation and intracellular signal transduction. Our results indicate that nanospearing does not result in the activation of naive primary B lymphocytes nor alter survival in ex vivo cultures. Herein, B cells exposed to CNTs were capable of responding to extrinsic pro-survival signals such as interleukin-4 and signaling by the B-cell antigen receptor in a manner similar to that of B cells cultured in the absence of CNTs. Our study demonstrates the biocompatibility of the CNT-mediated nanospearing procedure with respect to primary B lymphocytes.

  13. 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

    Studies reporting beneficial effects of B lymphocytes in autoimmune diseases have been accumulating and a regulatory role for certain B cell subsets is hence getting more and more recognition. Recently, B cells were shown to exhibit a regulatory effect in a T cell transfer model of colitis. Here,...

  14. Circulating monocytes and B-lymphocytes in neovascular age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Hector SM

    2017-01-01

    Full Text Available Sven Magnus Hector,1 Torben Lykke Sørensen1,2 1Clinical Eye Research Unit, Zealand University Hospital, Roskilde, 2Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark Background: Individuals with neovascular age-related macular degeneration (AMD have altered number and distribution of retinal macrophages and show changes in circulating antibodies. We wanted to investigate the corresponding precursors, with subpopulations. We therefore measured monocyte and B-lymphocyte populations in individuals with neovascular AMD.Design: This was an observational case–control study.Participants or samples: A total of 31 individuals with neovascular AMD and 30 healthy age-matched controls were included.Methods: Patients and controls were interviewed, and ophthalmological examination included visual acuity assessment using the Early Treatment Diabetic Retinopathy Study (ETDRS chart, spectral domain optical coherence tomography (SD-OCT, slit-lamp examination and fundus photography. Moreover, venous blood was drawn and prepared for flow cytometry. Cells were gated and measured for surface markers.Main outcome measures: Relative amounts of monocytes and B-lymphocytes with subsets, as well as selected surface markers, were measured.Results: The two groups did not significantly differ in age, smoking history, body mass index, physical activity or C-reactive protein (CRP. Total monocytes (percentage of all leukocytes were lower in the neovascular AMD group (median 5.5% compared with the level in the control group (6.5%; P-value: 0.028. The percentage of intermediate monocytes positive for cluster of differentiation 11b (CD11b was lower for AMD patients (99.4% compared with 100% for the control group (P-value: 0.032.Conclusion: We observed lower numbers of monocytes, which show a potentially impaired ability to migrate across the endothelial wall in patients with neovascular AMD. These subtle changes could potentially lead to an

  15. Anergy in self-directed B lymphocytes from a statistical mechanics perspective

    CERN Document Server

    Agliari, Elena; Del Ferraro, Gino; Guerra, Francesco; Tantari, Daniele

    2012-01-01

    The ability of the adaptive immune system to discriminate between self and non-self mainly stems from the ontogenic clonal-deletion of lymphocytes expressing strong binding affinity with self-peptides. However, some self-directed lymphocytes may evade selection and still be harmless due to a mechanism called clonal anergy. As for B lymphocytes, two major explanations for anergy developed over three decades: according to "Varela theory", it stems from a proper orchestration of the whole B-repertoire, in such a way that self-reactive clones, due to intensive interactions and feed-back from other clones, display more inertia to mount a response. On the other hand, according to the `two-signal model", which has prevailed nowadays, self-reacting cells are not stimulated by helper lymphocytes and the absence of such signaling yields anergy. The first result we present, achieved through disordered statistical mechanics, shows that helper cells do not prompt the activation and proliferation of a certain sub-group of ...

  16. Anergy in self-directed B lymphocytes: A statistical mechanics perspective.

    Science.gov (United States)

    Agliari, Elena; Barra, Adriano; Del Ferraro, Gino; Guerra, Francesco; Tantari, Daniele

    2015-06-21

    Self-directed lymphocytes may evade clonal deletion at ontogenesis but still remain harmless due to a mechanism called clonal anergy. For B-lymphocytes, two major explanations for anergy developed over the last decades: according to Varela theory, anergy stems from a proper orchestration of the whole B-repertoire, such that self-reactive clones, due to intensive feed-back from other clones, display strong inertia when mounting a response. Conversely, according to the model of cognate response, self-reacting cells are not stimulated by helper lymphocytes and the absence of such signaling yields anergy. Through statistical mechanics we show that helpers do not prompt activation of a sub-group of B-cells: remarkably, the latter are just those broadly interacting in the idiotypic network. Hence Varela theory can finally be reabsorbed into the prevailing framework of the cognate response model. Further, we show how the B-repertoire architecture may emerge, where highly connected clones are self-directed as a natural consequence of ontogenetic learning.

  17. Immunostimulant activity of noni (Morinda citrifolia) on T and B lymphocytes.

    Science.gov (United States)

    Nayak, Smita; Mengi, Sushma

    2010-07-01

    Morinda citrifolia Linn (Rubiaceae) is a traditional medicinal herb that has been purported to be beneficial in the treatment of infections due to its immune enhancing properties. However, detailed studies highlighting the effect of different compounds isolated from the plant on the immune system are lacking. In this study, the stimulatory effects of the extracts and fractions of M. citrifolia fruits on important components of the adaptive immune system such as T lymphocytes and B lymphocytes were studied. The effects of the plant extracts on lymphocytes were assessed by in vitro (MTT assay) and in vivo (cell mediated immune response) techniques. Results of the MTT study indicated that the hydroalcoholic (0.5 and 1.0 mg/mL) and aqueous extracts (0.5 and 1.0 mg/mL) significantly (p citrifolia fruits on B-cells was measured by the delayed type hypersensitivity method. The study revealed that the hydroalcoholic extract (200 mg/kg) and fraction F I (40 mg/kg) significantly increased the humoral response to the extent of 33.33 and 35.12%, respectively. The results of this study confirm the cellular and humoral immunostimulant properties of M. citrifolia fruits and justify its usage in traditional medicine.

  18. T and B lymphocytes in the marmoset: a natural haemopoietic chimera

    Energy Technology Data Exchange (ETDEWEB)

    Niblack, G.D.; Gengozian, N.

    1976-01-01

    The thymus-derived (T) lymphocyte and bone marrow-derived (B) lymphocyte populations of the marmoset were characterized using specific cell surface markers. Approximately 85% of the thymocytes formed rosettes with neuraminidase-treated sheep erythrocytes (E/sub n/). The percentage (approximately 69%) of peripheral blood lymphocytes (PBL) forming rosettes with E/sub n/ was the same as that which stained with fluorescently labelled goat anti-marmoset thymocyte serum (ATS). These two assays identified the same cell population since treatment of cells with ATS and complement resulted in a concomitant decrease in E/sub n/ rosette formation. Marmoset PBL also formed rosettes with human erythrocytes sensitized with antibody and complement (HEAC); since the percentage (approximately 20%) HEAC rosette was the same as that of cells stained with fluorescently labelled goat anti-marmoset IgG, these cells were considered to be B cells. A small percentage of cells (aproximately 1.5%) possessed both types of receptors. The mean percentages of T and B cells present in PBL of single-born, presumably non-chimeric animals, were the same as that of isosexual and heterosexual chimeras.

  19. CR2-mediated activation of the complement alternative pathway results in formation of membrane attack complexes on human B lymphocytes

    DEFF Research Database (Denmark)

    Nielsen, C H; Marquart, H V; Prodinger, W M;

    2001-01-01

    Normal human B lymphocytes activate the alternative pathway of complement via complement receptor type 2 (CR2, CD21), that binds hydrolysed C3 (iC3) and thereby promotes the formation of a membrane-bound C3 convertase. We have investigated whether this might lead to the generation of a C5...... convertase and consequent formation of membrane attack complexes (MAC). Deposition of C3 fragments and MAC was assessed on human peripheral B lymphocytes in the presence of 30% autologous serum containing 4.4 mM MgCl2/20 mM EGTA, which abrogates the classical pathway of complement without affecting...... the alternative pathway. Blockade of the CR2 ligand-binding site with the monoclonal antibody FE8 resulted in 56 +/- 13% and 71 +/- 9% inhibition of the C3-fragment and MAC deposition, respectively, whereas the monoclonal antibody HB135, directed against an irrelevant CR2 epitope, had no effect. Blockade...

  20. 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.

  1. Differential regulation of voltage- and calcium-activated potassium channels in human B lymphocytes.

    Science.gov (United States)

    Partiseti, M; Choquet, D; Diu, A; Korn, H

    1992-06-01

    The expression and characteristics of K+ channels of human B lymphocytes were studied by using single and whole-cell patch-clamp recordings. They were gated by depolarization (voltage-gated potassium current, IKv, 11-20 pS) and by an increase in intracellular Ca2+ concentration (calcium-activated potassium current, IKCa, 26 pS), respectively. The level of expression of these channels was correlated with the activational status of the cell. Both conductances are blocked by tetraethylammonium, verapamil, and charybdotoxin, and are insensitive to apamin; 4-aminopyridine blocks IK, preferentially. We used a protein kinase C activator (PMA) or antibodies to membrane Ig (anti-mu) to activate resting splenocytes in culture. Although IKv was recorded in the majority of the resting lymphocytic population, less than 20% of the activated cells expressed this conductance. However, in this subset the magnitude of IKv was 20-fold larger than in resting cells. On the other hand, IKCa was detected in nearly one half of the resting cells, whereas all activated cells expressed this current. The magnitude of IKCa was, on average, 30 times larger in activated than in nonactivated cells. These results probably reflect that during the course of activation 1) the number of voltage-dependent K+ channels per cell decreases and increases in a small subset and 2) the number of Ca(2+)-dependent K+ channels per cell increases in all cells. We suggest that the expression of functional Ca(2+)- and voltage-activated K+ channels are under the control of different regulatory signals.

  2. The peripheral blood compartment in patients with Graves' disease: activated T lymphocytes and increased transitional and pre-naive mature B lymphocytes

    Science.gov (United States)

    Van der Weerd, K; Van Hagen, P M; Schrijver, B; Kwekkeboom, D J; De Herder, W W; Ten Broek, M R J; Postema, P T E; Van Dongen, J J M; Staal, F J T; Dik, W A

    2013-01-01

    Graves' disease (GD) is an autoimmune disease that involves aberrant B and T lymphocyte responses. Detailed knowledge about lymphocyte subpopulation composition will therefore enhance our understanding of the pathogenesis of GD and might support the development of new immunomodulatory treatment approaches. The aim of this study was to gain detailed insight into the composition of the peripheral blood lymphocyte compartment in GD before and during anti-thyroid drug therapy. Major B and T lymphocyte subpopulations were investigated by flow cytometry in peripheral blood from newly diagnosed GD patients (n = 5), GD patients treated with anti-thyroid drugs (n = 4), patients with recurrent GD (n = 7) and healthy controls (HC; n = 10). In GD patients, numbers of activated T lymphocytes [human leucocyte antigen D-related (HLA-DR)+ and CD25+] were increased. The B lymphocyte compartment in GD was characterized by significantly higher numbers of transitional (CD38highCD27−, P < 0·03) and pre-naive mature (CD38lowCD27−IgD+CD5+, P < 0·04) B lymphocytes, while memory populations were slightly decreased. The increased numbers of CD5+, transitional and pre-naive mature B lymphocytes correlated positively with fT4 plasma levels. GD is associated with increased numbers of activated T lymphocytes and transitional and pre-naive mature CD5+ B lymphocytes within the peripheral blood. The increase in CD5+ B lymphocytes was due mainly to an increase in transitional and pre-naive mature B lymphocytes. Increased fT4 plasma levels might be associated with this increase in transitional and pre-naive mature CD5+ B lymphocytes. PMID:23901889

  3. Human CD38hiCD138⁺ plasma cells can be generated in vitro from CD40-activated switched-memory B lymphocytes.

    Science.gov (United States)

    Maïga, Rayelle Itoua; Bonnaure, Guillaume; Rochette, Josiane Tremblay; Néron, Sonia

    2014-01-01

    B lymphocyte differentiation into long-lived plasma cells is the keystone event for the production of long-term protective antibodies. CD40-CD154 and CD27-CD70 interactions are involved in human B lymphocyte differentiation into CD38(hi)CD138(+) cells in vivo as well as in vitro. In this study, we have compared these interactions in their capacity to drive switched-memory B lymphocytes differentiation into CD38(hi)CD138(+) plasma cells. The targeted B lymphocytes were isolated from human peripheral blood, expanded for 19 days, and then submitted to CD70 or CD154 interactions for 14 days. The expanded B lymphocytes were constitutively expressing CD39, whereas CD31's expression was noticed only following the in vitro differentiation step (day 5) and was exclusively present on the CD38(hi) cell population. Furthermore, the generated CD38(hi)CD138(+) cells showed a higher proportion of CD31(+) cells than the CD38(hi)CD138(-) cells. Besides, analyses done with human blood and bone marrow plasma cells showed that in vivo and de novo generated CD38(hi)CD138(+) cells have a similar CD31 expression profile but are distinct according to their reduced CD39 expression level. Overall, we have evidences that in vitro generated plasma cells are heterogeneous and appear as CD39(+) precursors to the ones present in bone marrow niches.

  4. 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......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...... reaction (PCR) using in addition a degenerate kappa light chain signal peptide region primer. The PCR product was cloned into the M13mp18 phage. The cloning efficiency was 100-600 clones/ml of blood. Of the 86 clones sequenced, 90% represented rearranged kappa light chain genes from different antibody...

  5. Unexpected and persistent depletion of B lymphocytes CD20 following a minimum dose of anti-CD20 antibody (Rituximab

    Directory of Open Access Journals (Sweden)

    V. Bruzzese

    2011-06-01

    Full Text Available Rituximab is a chemeric murine/human anti-B lymphocyte antigen CD20 monoclonal antibody used in the treatment of rheumatoid arthritis resistant to treatment by one or more anti TNF-alpha therapies (1. The recommended dose for an efficient depletion of the B CD 20 lymphocytes in rheumatoid arthritis is two infusions of 1000 mg, with the second infusion being administered two weeks after the first. At this dose, one obtains a rapid and persistent depletion of CD 20 cells, with repopulation occurring, on the average, in about eight months (2. Here, we present a case of a woman treated with only 50 mg of rituximab, who underwent both a rapid and pronounced reduction of B CD 20 lymphocytes...

  6. 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...

  7. Bone Marrow Mesenchymal Stem Cells Enhance the Differentiation of Human Switched Memory B Lymphocytes into Plasma Cells in Serum-Free Medium

    Science.gov (United States)

    Gervais-St-Amour, Catherine

    2016-01-01

    The differentiation of human B lymphocytes into plasma cells is one of the most stirring questions with regard to adaptive immunity. However, the terminal differentiation and survival of plasma cells are still topics with much to be discovered, especially when targeting switched memory B lymphocytes. Plasma cells can migrate to the bone marrow in response to a CXCL12 gradient and survive for several years while secreting antibodies. In this study, we aimed to get closer to niches favoring plasma cell survival. We tested low oxygen concentrations and coculture with mesenchymal stem cells (MSC) from human bone marrow. Besides, all cultures were performed using an animal protein-free medium. Overall, our model enables the generation of high proportions of CD38+CD138+CD31+ plasma cells (≥50%) when CD40-activated switched memory B lymphocytes were cultured in direct contact with mesenchymal stem cells. In these cultures, the secretion of CXCL12 and TGF-β, usually found in the bone marrow, was linked to the presence of MSC. The level of oxygen appeared less impactful than the contact with MSC. This study shows for the first time that expanded switched memory B lymphocytes can be differentiated into plasma cells using exclusively a serum-free medium. PMID:27872867

  8. Primary B Lymphocytes Infected with Kaposi's Sarcoma-Associated Herpesvirus Can Be Expanded In Vitro and Are Recognized by LANA-Specific CD4+ T Cells

    Science.gov (United States)

    Nicol, Samantha M.; Sabbah, Shereen; Brulois, Kevin F.; Jung, Jae U.; Bell, Andrew I.

    2016-01-01

    ABSTRACT Kaposi's sarcoma-associated herpesvirus (KSHV) has tropism for B lymphocytes, in which it establishes latency, and can also cause lymphoproliferative disorders of these cells manifesting as primary effusion lymphoma (PEL) and multicentric Castleman disease (MCD). T cell immunity is vital for the control of KSHV infection and disease; however, few models of B lymphocyte infection exist to study immune recognition of such cells. Here, we developed a model of B lymphocyte infection with KSHV in which infected tonsillar B lymphocytes were expanded by providing mitogenic stimuli and then challenged with KSHV-specific CD4+ T cells. The infected cells expressed viral proteins found in PELs, namely, LANA and viral IRF3 (vIRF3), albeit at lower levels, with similar patterns of gene expression for the major latency, viral interleukin 6 (vIL-6), and vIRF3 transcripts. Despite low-level expression of open reading frame 50 (ORF50), transcripts for the immune evasion genes K3 and K5 were detected, with some downregulation of cell surface-expressed CD86 and ICAM. The vast majority of infected lymphocytes expressed IgM heavy chains with Igλ light chains, recapitulating the features seen in infected cells in MCD. We assessed the ability of the infected lymphocytes to be targeted by a panel of major histocompatibility complex (MHC) class II-matched CD4+ T cells and found that LANA-specific T cells restricted to different epitopes recognized these infected cells. Given that at least some KSHV latent antigens are thought to be poor targets for CD8+ T cells, we suggest that CD4+ T cells are potentially important effectors for the in vivo control of KSHV-infected B lymphocytes. IMPORTANCE KSHV establishes a latent reservoir within B lymphocytes, but few models exist to study KSHV-infected B cells other than the transformed PEL cell lines, which have likely accrued mutations during the transformation process. We developed a model of KSHV-infected primary B lymphocytes that

  9. 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.

  10. Expression and purification of a soluble B lymphocyte stimulator mutant modified with the T-helper cell epitope.

    Science.gov (United States)

    Gao, Huiguang; Fu, Weiling; Li, Rongfen; Chen, Linfeng; Ji, Qing; Zhang, Li; Huang, Gang; He, Fengtian

    2006-10-01

    The DNA encoding soluble B lymphocyte stimulator (134-285 amino acids, sBLyS) mutant with residues 217-224 replaced by two glycines (named msBLyS) was constructed. The sequence encoding a foreign immunodominant T-helper epitope from ovalbumin (OVA) was then coupled to the 5'-end of msBLyS cDNA. After being sequenced, the recombinant DNA was ligated into the prokaryotic expression vector pQE-80L. The recombinant protein was produced in E. coli DH5alpha after induction with IPTG with the yield of more than 40% of total bacterial protein. The recombinant protein was purified with Ni-NTA chromatography and Sepharcryl S200 chromatography to a purity of more than 98%. The BALB/c mice, immunized with the recombinant protein, produced anti-BLyS antibodies at a high level, which indicated that the recombinant BLyS mutant modified with T-helper epitope elicited polyclonal antibodies with cross-reactivity with BLyS in vivo. This recombinant protein may therefore be used as immune inhibitor of BLyS for treating BLyS -associated autoimmune diseases.

  11. An optimized B lymphocyte stimulator (BLyS) antagonist peptide inhibits the interaction of BLyS with BCMA.

    Science.gov (United States)

    Tian, Yu; Zhu, Yan-Feng; Wu, Zhen; Feng, Jian-Nan; Li, Yan; Shen, Bei-Fen; Sun, Jian

    2013-04-01

    B lymphocyte stimulator (BLyS) antagonists are new therapeutic reagents for treating the autoimmune diseases. Peptibodies can inhibit the bioactivity of BLyS, the same as other BLyS antagonists: decoyed BLyS receptors and anti-BLyS antibodies. In this study, a new optimized BLyS antagonist peptide was designed according to our previous work by the computer-aided homology modeling. Competitive ELISA showed that the peptide at 100 μg/ml could inhibit 54 % of the BCMA-Fc binding to BLyS. To maintain its stability and spatial conformation, the peptide was fused to human IgG1 Fc to form a peptide-Fc fusion protein-a novel peptibody by gene engineering. ELISA indicated that the peptibody could bind with BLyS in dosage-dependent manner as BCMA-Fc did. This study highlights the possibility of designing and optimizing BLyS antagonist peptides with high biopotency by the computer-aided design. Thus, these peptides could neutralize BLyS activity and be potential antagonists to treat autoimmune diseases related with BLyS overexpression.

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

    Directory of Open Access Journals (Sweden)

    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.

  13. Decreased Frequency of Circulating Myelin Oligodendrocyte Glycoprotein B Lymphocytes in Patients with Relapsing-Remitting Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Annie Elong Ngono

    2015-01-01

    Full Text Available Although there is no evidence for a role of anti-MOG antibodies in adult MS, no information on B lymphocytes with MOG-committed BCR is available. We report here on the frequency of anti-MOG B cells forming rosettes with polystyrene beads (BBR covalently bound to the extracellular domain of rhMOG in 38 relapsing-remitting patients (RRMS and 50 healthy individuals (HI. We show a substantial proportion of circulating anti-MOG-BBR in both RRMS and HI. Strikingly, MOG-specific B cells frequencies were lower in MS than in HI. Anti-MOG antibodies measured by a cell-based assay were not different between MS patients and controls, suggesting a specific alteration of anti-MOG B cells in MS. Although anti-MOG-BBR were higher in CNS fluid than in blood, no difference was observed between MS and controls. Lower frequency of MOG-BBR in MS was not explained by an increased apoptosis, but a trend for lower proliferative capacity was noted. Despite an efficient B cell transmigration across brain derived endothelial cells, total and anti-MOG B cells transmigration was similar between MS and HI. The striking alteration in MOG-specific B cells, independent of anti-MOG antibody titers, challenges our view on the role of MOG-specific B cells in MS.

  14. B Lymphocyte Stimulator (BLyS) Is Expressed in Human Adipocytes In Vivo and Is Related to Obesity but Not to Insulin Resistance

    OpenAIRE

    Nike Müller; Schulte, Dominik M.; Susann Hillebrand; Kathrin Türk; Jochen Hampe; Clemens Schafmayer; Mario Brosch; Witigo von Schönfels; Markus Ahrens; Rainald Zeuner; Schröder, Johann O.; Matthias Blüher; Christian Gutschow; Sandra Freitag-Wolf; Marta Stelmach-Mardas

    2014-01-01

    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 ...

  15. Targeting of chemical mutagens to differentiating B-lymphocytes in vivo: detection by direct DNA labeling and sister chromatid exchange induction

    Energy Technology Data Exchange (ETDEWEB)

    Bloom, S.E.; Nanna, U.C.; Dietert, R.R.

    1987-01-01

    In vivo systems for analyzing mutagen interactions with a specific differentiating cell population are rare. Taking advantage of the unique anatomical features of the bursa of Fabricius in the chicken, the authors explored the possibility of targeting chemical mutagens to a defined differentiating cell population in the animal, namely, the B-lymphocytes series. Such cells are known to be the targets for the oncogene-activating avian leukosis virus. Targeting of chemicals to cells of the bursa was demonstrated by application of the DNA-specific fluorochrome 4'-6-diamidino-2-phenylindole (DAPI) to the anal lips of neonatal chicks. Bright nuclear fluorescence of cells in the bursa demonstrated to occur within minutes after the application of 500..mu..l of DAPI. DAPI labeling of nuclei was detected up to several days after a single application. No nuclear labeling was exhibited in cells of neighboring tissues. Methyl methanesulfonate (MMS)(10..mu..l) was applied to the anal lips of day-old chicks to study dose-response kinetics for mutagen targeting to DNA of dividing B-lymphocytes in the bursa. Since the mitotic index was found to be quite high (25-30%) in the bursa, chromosome analysis was used to assay for genome damage. Sister chromatid exchange frequencies of 3.9, 7.3, and 9.0 (baseline 2.5) per cell were obtained at MMS dosages per animal of 50 ..mu..g, 100..mu..g, and 200..mu..g, respectively. These results indicate the rapid and quantitative localization of DNA-binding chemicals to cells of the bursa, particularly the resident B-lymphocytes. The bursa should be a useful system for studying mutagen-DNA interactions in the differentiating B-lymphocyte and subsequent influences on the development of immunity and lymphoproliferative disease.

  16. Inhibition of antigen receptor-dependent Ca(2+) signals and NF-AT activation by P2X7 receptors in human B lymphocytes.

    Science.gov (United States)

    Pippel, Anja; Beßler, Björn; Klapperstück, Manuela; Markwardt, Fritz

    2015-04-01

    One of the first intracellular signals after antigen binding by the antigen receptor of B lymphocytes is the increased intracellular Ca(2+) concentration ([Ca(2+)]i), which is followed by several intracellular signaling events like the nuclear translocation of the transcription factor NF-AT controlling the fate of B lymphocytes after their activation. Extracellular ATP, which is released from cells under several pathological conditions, is considered a danger-associated signal serving as an immunomodulator. We investigated the interaction of antigen receptor (BCR) and P2X7 receptor (P2X7R) activation on [Ca(2+)]i signaling and on nuclear translocation of the transcription factor NF-AT in human B lymphocytes. Although the P2X7R is an ATP-gated Ca(2+)-permeable ion channel, P2X7R activation inhibits the BCR-mediated [Ca(2+)]i responses. This effect is mimicked by cell membrane depolarization induced by an increase in the extracellular K(+) concentration or by application of the Na(+) ionophore gramicidin, but is abolished by stabilization of the membrane potential using the K(+) ionophore valinomycin, by extracellular Mg(2+), which is known to inhibit P2X7R-dependent effects, or by replacing Na(+) by the less P2X7R-permeable Tris(+) ion. Furthermore, P2X7R activation by ATP inhibits the BCR-dependent translocation of the transcription factor NF-ATc1 to the nucleus. We therefore conclude that extracellular ATP via the P2X7R mediates inhibitory effects on B cell activation. This may be of relevance for understanding of the activation of the BCR under pathological conditions and for the development of therapeutic strategies targeting human B lymphocytes or P2X7 receptors.

  17. 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

  18. CCR7 is mainly expressed in teleost gills, where it defines an IgD+IgM- B lymphocyte subset.

    Science.gov (United States)

    Castro, Rosario; Bromage, Erin; Abós, Beatriz; Pignatelli, Jaime; González Granja, Aitor; Luque, Alfonso; Tafalla, Carolina

    2014-02-01

    Chemokine receptor CCR7, the receptor for both CCL19 and CCL21 chemokines, regulates the recruitment and clustering of circulating leukocytes to secondary lymphoid tissues, such as lymph nodes and Peyer's patches. Even though teleost fish do not have either of these secondary lymphoid structures, we have recently reported a homolog to CCR7 in rainbow trout (Oncorhynchus mykiss). In the present work, we have studied the distribution of leukocytes bearing extracellular CCR7 in naive adult tissues by flow cytometry, observing that among the different leukocyte populations, the highest numbers of cells with membrane (mem)CCR7 were recorded in the gill (7.5 ± 2% CCR7(+) cells). In comparison, head kidney, spleen, thymus, intestine, and peripheral blood possessed CCR7(+) cells. When CCR7 was studied at early developmental stages, we detected a progressive increase in gene expression and protein CCR7 levels in the gills throughout development. Surprisingly, the majority of the CCR7(+) cells in the gills were not myeloid cells and did not express membrane CD8, IgM, nor IgT, but expressed IgD on the cell surface. In fact, most IgD(+) cells in the gills expressed CCR7. Intriguingly, the IgD(+)CCR7(+) population did not coexpress memIgM. Finally, when trout were bath challenged with viral hemorrhagic septicemia virus, the number of CCR7(+) cells significantly decreased in the gills while significantly increased in head kidney. These results provide evidence of the presence of a novel memIgD(+)memIgM(-) B lymphocyte subset in trout that expresses memCCR7 and responds to viral infections. Similarities with IgD(+)IgM(-) subsets in mammals are discussed.

  19. 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.

  20. Dual functions of interferon regulatory factors 7C in Epstein-Barr virus-mediated transformation of human B lymphocytes.

    Directory of Open Access Journals (Sweden)

    Yong Zhao

    Full Text Available Epstein-Barr virus (EBV infection is associated with several human malignancies. Interferon (IFN regulatory factor 7 (IRF-7 has several splicing variants, and at least the major splicing variant (IRF-7A has oncogenic potential and is associated with EBV transformation processes. IRF-7C is an alternative splicing variant with only the DNA-binding domain of IRF-7. Whether IRF-7C is present under physiological conditions and its functions in viral transformation are unknown. In this report, we prove the existence of IRF-7C protein and RNA in certain cells under physiological conditions, and find that high levels of IRF-7C are associated with EBV transformation of human primary B cells in vitro as well as EBV type III latency. EBV latent membrane protein 1 (LMP-1 stimulates IRF-7C expression in B lymphocytes. IRF-7C has oncogenic potential in rodent cells and partially restores the growth properties of EBV-transformed cells under a growth-inhibition condition. A tumor array experiment has identified six primary tumor specimens with high levels of IRF-7C protein--all of them are lymphomas. Furthermore, we show that the expression of IRF-7C is apparently closely associated with other IRF-7 splicing variants. IRF-7C inhibits the function of IRF-7 in transcriptional regulation of IFN genes. These data suggest that EBV may use splicing variants of IRF-7 for its transformation process in two strategies: to use oncogenic properties of various IRF-7 splicing variants, but use one of its splicing variants (IRF-7C to block the IFN-induction function of IRF-7 that is detrimental for viral transformation. The work provides a novel relation of host/virus interactions, and has expanded our knowledge about IRFs in EBV transformation.

  1. [B lymphocyte ontogeny].

    Science.gov (United States)

    Balandrán, Juan Carlos; Pelayo, Rosana

    2016-01-01

    The B cell development from hematopoietic stem cells is a continuous and highly regulated process where multiple differentiation potentials are gradually lost while acquiring lineage specialized functions. At 50 years of the B cell discovery, the current knowledge of its early differentiation largely derive from the isolation and characterization of bone marrow early progenitor cells initiating the lymphoid program, and from the definition of transcriptional activity patterns that control cell fate decisions. Of particular relevance has been the intercommunication between B cell precursors and key components of the hematopoietic microenvironment, both for generation of novel models integrating all regulatory elements of this complex process, and for the understanding of this branch of the adaptive immune system in disease settings. This review provides an overview of the complex process of lymphoid differentiation: from the hierarchical organization and biological characteristics of primitive cells involved in its earliest stages, to the principles governing its interdependence with the hematopoietic microenvironment.

  2. Alterations in sensitivity to estrogen, dihydrotestosterone, and xenogens in B-lymphocytes from children with autism spectrum disorder and their unaffected twins/siblings.

    Science.gov (United States)

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

    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. 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 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  4. Multiparameter flow cytometry to detect hematogones and to assess B-lymphocyte clonality in bone marrow samples from patients with non-Hodgkin lymphomas

    Directory of Open Access Journals (Sweden)

    Giovanni Carulli

    2014-06-01

    Full Text Available Hematogones are precursors of B-lymphocytes detected in small numbers in the bone marrow. Flow cytometry is the most useful tool to identify hematogones and, so far, 4-color methods have been published. In addition, flow cytometry is used in the diagnosis and follow-up of lymphomas. We developed a flow cytometric 7-color method to enumerate hematogones and to assess B-lymphocyte clonality for routine purposes. We evaluated 171 cases of B-cell non-Hodgkin lymphomas, either at diagnosis or in the course of follow-up. By our diagnostic method, which was carried out by the combination K/l/CD20/CD19/CD10/CD45/CD5, we were able to detect hematogones in 97.6% of samples and to distinguish normal B-lymphocytes, neoplastic lymphocytes and hematogones in a single step. The percentage of hematogones showed a significant inverse correlation with the degree of neoplastic infiltration and, when bone marrow samples not involved by disease were taken into consideration, resulted higher in patients during follow-up than in patients evaluated at diagnosis.

  5. Progression in the study on the phagocytosis function of B lymphocyte%B淋巴细胞吞噬功能研究进展

    Institute of Scientific and Technical Information of China (English)

    高杨; 高继鑫; 刘玉峰

    2009-01-01

    以往的观点认为只有巨噬细胞、单核细胞、粒细胞和树突状细胞是专职的吞噬细胞,而B细胞作为免疫系统的抗体产生细胞,虽然能够产生特异的免疫球蛋白与抗原结合,却不具备吞噬能力.但最近的研究指出硬骨鱼类(彩虹鳟鱼)和两栖类(爪蟾)的B细胞可以吞噬颗粒抗原,首次揭示了进化上较为原始的B细胞同样具有吞噬能力.众多研究提示哺乳动物B-1 B细胞很可能具有吞噬能力.%It was accepted in the past that only these cells such as macrophage, histoleucocyte, granular cell and dendritic cell are phagocytes, while B lymphocyte has no ability to phagocytize, although it can generate specific immune globulin for antigen binding. However recent studies indicate that B lymphocyte of osteichthyes (trout) and amphibia (xenopus laevis) can phagocytize particulate antigen, these studies for the first time re-vealed that relatively archaic B lymphocyte has ability to phagocytize too. Numerous studies reveal that B-1 cell in mammalian probably has ability to phagocytize.

  6. B淋巴细胞在心血管疾病中的作用%The role of B lymphocytes in cardiovascular diseases

    Institute of Scientific and Technical Information of China (English)

    迟迪; 孙勇; 李阳; 刘向兰; 朱静怡; 曹瑞; 于波; 吴健

    2016-01-01

    B淋巴细胞来源于骨髓多能干细胞,通过分泌抗体、提呈抗原,提供协同刺激信号及分泌细胞因子等方式在体液免疫应答过程中发挥重要功能.现有证据表明,B淋巴细胞的成熟,活化,以及分泌抗体等作用可以对心血管系统产生重要影响.本文综合近期的研究,对B淋巴细胞在冠心病、心力衰竭以及扩张型心肌病中的作用及其机制进行综述.%B lymphocytes derive from bone marrow pluripotent stem cells,they play an important role in the process of humoral immune response by secreting antibodies,presenting antigens,providing costimulating signals and secre- ting cytokines etc.Existing evidence demonstrates that maturation,activation and antibody secretion effects of B lymphocytes have important influence on cardiovascular system.The present article synthesize recent researches, made a review about effect and its mechanisms of B lymphocytes in coronary heart disease,heart failure and dilated cardiomyopathy.

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

    Directory of Open Access Journals (Sweden)

    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.

  8. Effect of radiation on cell interactions with respect to the phenomenon of inactivation on non-syngeneic stem cells. A radiation-induced change in B-lymphocyte function

    Energy Technology Data Exchange (ETDEWEB)

    Petrov, R.V.; Dozmorov, I.M.; Lutsenko, G.V.; Nikolaeva, I.S.; Rudneva, T.B. (Institut Biofiziki, Moscow (USSR))

    A study was made of the changes in the mode of interaction between T- and B-lymphocytes of mouse lymph nodes with respect to the phenomenon of inactivation of non-syngeneic haemopoietic stem cells. It was shown that irradiation of B-lymphocytes with doses of 77.4-232.2 mC/kg changes their helper activity into a suppressor activity with regard to T-cell-killers having a low electrophoretic mobility.

  9. 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...... reviewing the efficacy and safety in other autoimmune diseases, we propose that treatment with the B cell-depleting agent Rituximab may become a clinically relevant treatment option in selected cases of GD, particularly when complicated with thyroid-associated ophthalmopathy....

  10. The classical and alternative pathways of complement activation play distinct roles in spontaneous C3 fragment deposition and membrane attack complex (MAC) formation on human B lymphocytes

    DEFF Research Database (Denmark)

    Leslie, Robert Graham Quinton; Nielsen, Claus Henrik

    2004-01-01

    The contributions of the classical (CP) and alternative (AP) pathways of complement activation to the spontaneous deposition of C3 fragments and the formation of membrane attack complexes (MAC) on human B lymphocytes, were assessed by incubating peripheral blood mononuclear cells with autologous ...... of MAC formation was also found to be highly pathway dependent, with the AP being about 15-fold more efficient at initiating this process than the CP. A model accounting for the effectiveness of the AP in both preserving C3 fragment integrity and initiating MAC is presented....

  11. Involvement of suppressive B-lymphocytes in the mechanism of tolerogenic dendritic cell reversal of type 1 diabetes in NOD mice.

    Science.gov (United States)

    Di Caro, Valentina; Phillips, Brett; Engman, Carl; Harnaha, Jo; Trucco, Massimo; Giannoukakis, Nick

    2014-01-01

    The objective of the study was to identify immune cell populations, in addition to Foxp3+ T-regulatory cells, that participate in the mechanisms of action of tolerogenic dendritic cells shown to prevent and reverse type 1 diabetes in the Non-Obese Diabetic (NOD) mouse strain. Co-culture experiments using tolerogenic dendritic cells and B-cells from NOD as well as transgenic interleukin-10 promoter-reporter mice along with transfer of tolerogenic dendritic cells and CD19+ B-cells into NOD and transgenic mice, showed that these dendritic cells increased the frequency and numbers of interleukin-10-expressing B-cells in vitro and in vivo. The expansion of these cells was a consequence of both the proliferation of pre-existing interleukin-10-expressing B-lymphocytes and the conversion of CD19+ B-lymphcytes into interleukin-10-expressing cells. The tolerogenic dendritic cells did not affect the suppressive activity of these B-cells. Furthermore, we discovered that the suppressive murine B-lymphocytes expressed receptors for retinoic acid which is produced by the tolerogenic dendritic cells. These data assist in identifying the nature of the B-cell population increased in response to the tolerogenic dendritic cells in a clinical trial and also validate very recent findings demonstrating a mechanistic link between human tolerogenic dendritic cells and immunosuppressive regulatory B-cells.

  12. Involvement of suppressive B-lymphocytes in the mechanism of tolerogenic dendritic cell reversal of type 1 diabetes in NOD mice.

    Directory of Open Access Journals (Sweden)

    Valentina Di Caro

    Full Text Available The objective of the study was to identify immune cell populations, in addition to Foxp3+ T-regulatory cells, that participate in the mechanisms of action of tolerogenic dendritic cells shown to prevent and reverse type 1 diabetes in the Non-Obese Diabetic (NOD mouse strain. Co-culture experiments using tolerogenic dendritic cells and B-cells from NOD as well as transgenic interleukin-10 promoter-reporter mice along with transfer of tolerogenic dendritic cells and CD19+ B-cells into NOD and transgenic mice, showed that these dendritic cells increased the frequency and numbers of interleukin-10-expressing B-cells in vitro and in vivo. The expansion of these cells was a consequence of both the proliferation of pre-existing interleukin-10-expressing B-lymphocytes and the conversion of CD19+ B-lymphcytes into interleukin-10-expressing cells. The tolerogenic dendritic cells did not affect the suppressive activity of these B-cells. Furthermore, we discovered that the suppressive murine B-lymphocytes expressed receptors for retinoic acid which is produced by the tolerogenic dendritic cells. These data assist in identifying the nature of the B-cell population increased in response to the tolerogenic dendritic cells in a clinical trial and also validate very recent findings demonstrating a mechanistic link between human tolerogenic dendritic cells and immunosuppressive regulatory B-cells.

  13. Expression of TLR-7, MyD88, NF-kB and INF-α in B lymphocytes of Mayan Women with Systemic Lupus Erythematosus, in Mexico

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    Guillermo eValencia Pacheco

    2016-02-01

    Full Text Available Background: Systemic Lupus Erythematosus (SLE is a chronic inflammatory autoimmune disease involving multiple organs. It is currently accepted that several genetic, environmental, and hormonal factors contributing to its development. Innate immunity may have a great influence in autoimmunity through Toll-like receptors (TLR. TLR-7 recognizing single-strand RNA has been involved in SLE. Its activation induces intracellular signal with attraction of MyD88 and NF-kB, leading to IFN-α synthesis which correlate with disease activity. Objective: To assess the expression of TLR-7, MyD88 and NF-kB in mononuclear cells of Mayan women with SLE. Methods: One hundred patients with SLE and one hundred healthy controls, all them Mayan women, were included. TLR-7 was analyzed on B and T lymphocytes, and MyD88 and NF-kB only in B lymphocytes. Serum INF-α level was evaluated by ELISA. Results: Significant expression (p < 0.0001 of TLR-7 in B and T lymphocytes and serum IFN-α increased (p = 0.034 was observed in patients. MyD88 and NF-kB were also increased in B lymphocytes of patients. TLR-7 and NF-kB expression correlated, but no correlation with INF-α and disease activity was detected. Conclusion: Data support the role of TLR-7 and signal proteins in the pathogenesis of SLE in the Mayan population of Yucatán.

  14. 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.

  15. Induction of heme oxygenase-1 in normal and malignant B lymphocytes by 15-deoxy-Δ12, 14-prostaglandin J2 requires Nrf2

    Science.gov (United States)

    Bancos, Simona; Baglole, Carolyn J.; Rahman, Irfan; Phipps, Richard P.

    2011-01-01

    Heme-oxygenase-1 (HO-1) is induced in response to oxidative stress and is believed to be a cytoprotective and anti-inflammatory enzyme. It is unknown whether normal or malignant human B lineage cells express HO-1. 15-deoxy-Δ12, 14-prostaglandin J2 (15d-PGJ2) is an interesting electrophilic lipid mediator able to increase oxidative stress in B cells. Here, we tested normal and malignant human B lineage cells for their ability to express HO-1 in response to 15d-PGJ2, as well as the signaling pathways required for HO-1 expression. 15d-PGJ2 potently induced HO-1 protein expression in normal and malignant B cells. Malignant B cells exhibited a greater induction of HO-1 protein compared to normal B lymphocytes. Using siRNA directed against the transcription factor Nrf2 and B cells isolated from Nrf2-deficient mice, we show that HO-1 induction by 15d-PGJ2 is dependent on Nrf2. These results show that, compared to normal B lymphocytes, malignant B cells have a greater capacity to increase their HO-1 protein levels in response to 15d-PGJ2. We speculate that the ability to highly express HO-1 by malignant B cells could confer a survival advantage. PMID:20064636

  16. Induction of heme oxygenase-1 in normal and malignant B lymphocytes by 15-deoxy-Delta(12,14)-prostaglandin J(2) requires Nrf2.

    Science.gov (United States)

    Bancos, Simona; Baglole, Carolyn J; Rahman, Irfan; Phipps, Richard P

    2010-01-01

    Heme-oxygenase-1 (HO-1) is induced in response to oxidative stress and is believed to be a cytoprotective and anti-inflammatory enzyme. It is unknown whether normal or malignant human B-lineage cells express HO-1. 15-deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)) is an interesting electrophilic lipid mediator able to increase oxidative stress in B cells. Here, we tested normal and malignant human B-lineage cells for their ability to express HO-1 in response to 15d-PGJ(2), as well as the signaling pathways required for HO-1 expression. 15d-PGJ(2) potently induced HO-1 protein expression in normal and malignant B cells. Malignant B cells exhibited a greater induction of HO-1 protein compared to normal B lymphocytes. Using siRNA directed against the transcription factor Nrf2 and B cells isolated from Nrf2-deficient mice, we show that HO-1 induction by 15d-PGJ(2) is dependent on Nrf2. These results show that, compared to normal B lymphocytes, malignant B cells have a greater capacity to increase their HO-1 protein levels in response to 15d-PGJ(2). We speculate that the ability to highly express HO-1 by malignant B cells could confer a survival advantage.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  18. A proteomic investigation of B lymphocytes in an autistic family: a pilot study of exposure to natural rubber latex (NRL) may lead to autism.

    Science.gov (United States)

    Shen, Chen; Zhao, Xin-liang; Ju, Weina; Zou, Xiao-bing; Huo, Li-rong; Yan, Wu; Zou, Jun-hua; Yan, Guo-di; Jenkins, Edmund C; Brown, W Ted; Zhong, Nanbert

    2011-03-01

    Autism is a multi-factorial neurodevelopmental disorder. We have investigated the molecular mechanism involved in a Chinese family with autism by a proteomic approach. Antibody chips containing 500 spots of human protein antibodies were used to screen for differentially expressed proteins in the peripheral B lymphocytes between autistic and non-autistic siblings in this family. Four proteins relevant to immuno-pathway, including IKKα that was up-regulated and Tyk2, EIF4G1 and PRKCI that were down-regulated, were identified differentially expressed in autistic versus non-autistic siblings. Western blot analysis and reverse transcription quantitative polymerase chain reaction validated the differential expression of these four proteins. Based on the function of these differentially expressed proteins, relevant studies on immunoglobulin E (IgE) level, nuclear factor kappa B signaling activation and cell cycle were conducted in both autistic and non-autistic children of this family. Considering the fact that the family members were in close contact with natural rubber latex (NRL) and that IgE-mediated cross-reactions could be triggered by Hevea brasiliensis (Hev-b) proteins in NRL, we hypothesize that immune reactions triggered by close contact with NRL might influence the functions of B lymphocytes by altering expression of certain proteins identified in our experiments thus contributing to the occurrence of autism.

  19. Localization of T and B Lymphocytes to the White Pulp of the Spleen is Independent of L-, E-, and P-Selectin

    Directory of Open Access Journals (Sweden)

    Mitchell H. Grayson

    2003-01-01

    Full Text Available T and B cell interactions are thought to be of prime importance in the generation of a humoral immune response. These interactions are thought to take place in the secondary lymphoid organs. The largest of which is the spleen. While the pathways involved in lymphocyte migration into other secondary lymphoid organs have been unraveled, very little is understood about T and B cell migration to the spleen. We report that adoptively transferred T lymphocytes appear more rapidly within the lymphoid compartment of the spleen than do B lymphocytes. Indeed, half of the transferred T lymphocytes in the spleen appear within the white pulp by 1.4 hours. B lymphocytes take nearly 4.3 hours to achieve the same level of accumulation. In addition, T lymphocyte arrival is fucoidan sensitive, while B cells are not affected by this polysaccharide. Finally, we show that neither L-, E-, or P-selectin appears to play a significant role in the accumulation of lymphocytes in the white pulp.

  20. Vitamin D3 Suppresses Class II Invariant Chain Peptide Expression on Activated B-Lymphocytes: A Plausible Mechanism for Downregulation of Acute Inflammatory Conditions

    Directory of Open Access Journals (Sweden)

    Omar K. Danner

    2016-01-01

    Full Text Available Class II invariant chain peptide (CLIP expression has been demonstrated to play a pivotal role in the regulation of B cell function after nonspecific polyclonal expansion. Several studies have shown vitamin D3 helps regulate the immune response. We hypothesized that activated vitamin D3 suppresses CLIP expression on activated B-cells after nonspecific activation or priming of C57BL/6 mice with CpG. This study showed activated vitamin D3 actively reduced CLIP expression and decreased the number of CLIP+ B-lymphocytes in a dose and formulation dependent fashion. Flow cytometry was used to analyze changes in mean fluorescent intensity (MFI based on changes in concentration of CLIP on activated B-lymphocytes after treatment with the various formulations of vitamin D3. The human formulation of activated vitamin D (calcitriol had the most dramatic reduction in CLIP density at an MFI of 257.3 [baseline of 701.1 (P value = 0.01]. Cholecalciferol and alfacalcidiol had no significant reduction in MFI at 667.7 and 743.0, respectively. Calcitriol seemed to best reduce CLIP overexpression in this ex vivo model. Bioactive vitamin D3 may be an effective compliment to other B cell suppression therapeutics to augment downregulation of nonspecific inflammation associated with many autoimmune disorders. Further study is necessary to confirm these findings.

  1. 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

  2. 鸡盲肠扁桃体中B淋巴细胞的发育%Development of B lymphocytes in caecal tonsil of chicken

    Institute of Scientific and Technical Information of China (English)

    杨树宝; 张英楠; 高晶晶; 张延林; 杨丽华; 栾维民

    2009-01-01

    The occurrence,migration,tissue localization and quantity changes of IgM~+, IgG~+ and IgA~+ B lymphocytes in chicken caecal tonsil were examined using the IgM, IgG and IgA monoclonal antibodies by immunohistochemical method. The results showed that IgM~+ cells first appeared in caecal tonsil from em-bryonic on day 20, both IgG~+ and IgA~+ cells appeared at 1-day-old. B lymphocytes mainly distributed in lamina propria under epithelium before 4-day-old; B lymphocytes were mainly distributed in middle and su-perior part mucous layer, whereafter they uniformly distributed in the whole mucous layer. The germinal centers which were composed by B lymphocytes appeared in the lamina propria at 14-day-old, but clear-cut germinal centers resided in the middle and inferior part of lamina propria at 21-day-old,and there were nu-merous IgM~+, IgG~+ and IgA~+ cells in germinal centers. B lymphocytes kept increasing with the increase of age,and reached stable at 35-day-old. Among the three type cells,IgM~+ cells were the most and IgG~+ cells were the least all the time. The results confirmed that the humoral immune function of caecal tonsil in chicken strengthened quickly after hatching,and reached the mature level at 35-day-old.%通过免疫组织化学方法,应用IgM、IgG和IgA单克隆抗体研究了IgM~+、IgG~+和IgA~+B淋巴细胞在鸡盲肠扁桃体中的出现、迁移、组织定位分布以及数量变化规律等一系列发育过程.结果显示,IgM~+细胞在胚胎20日龄时开始出现,而IgG~+和IgA~+细胞均在雏鸡出壳后1日龄时出现.在定位分布变化上,4日龄之前,B淋巴细胞主要分布在黏膜上皮下固有层中;4~7日龄时,B淋巴细胞则主要分布在黏膜固有层的中上部区域,随后各日龄B淋巴细胞均匀地分布在黏膜固有层中;14日龄时,黏膜固有层中出现主要由B淋巴细胞组成的生发中心,21日龄时可见轮廓更清晰的生发中心存在于黏膜固有层中下部区域,并且生发中心

  3. Genomics based analysis of interactions between developing B-lymphocytes and stromal cells reveal complex interactions and two-way communication

    Directory of Open Access Journals (Sweden)

    Bryder David

    2010-02-01

    Full Text Available Abstract Background The use of functional genomics has largely increased our understanding of cell biology and promises to help the development of systems biology needed to understand the complex order of events that regulates cellular differentiation in vivo. One model system clearly dependent on the integration of extra and intra cellular signals is the development of B-lymphocytes from hematopoietic stem cells in the bone marrow. This developmental pathway involves several defined differentiation stages associated with specific expression of genes including surface markers that can be used for the prospective isolation of the progenitor cells directly from the bone marrow to allow for ex vivo gene expression analysis. The developmental process can be simulated in vitro making it possible to dissect information about cell/cell communication as well as to address the relevance of communication pathways in a rather direct manner. Thus we believe that B-lymphocyte development represents a useful model system to take the first steps towards systems biology investigations in the bone marrow. Results In order to identify extra cellular signals that promote B lymphocyte development we created a database with approximately 400 receptor ligand pairs and software matching gene expression data from two cell populations to obtain information about possible communication pathways. Using this database and gene expression data from NIH3T3 cells (unable to support B cell development, OP-9 cells (strongly supportive of B cell development, pro-B and pre-B cells as well as mature peripheral B-lineage cells, we were able to identify a set of potential stage and stromal cell restricted communication pathways. Functional analysis of some of these potential ways of communication allowed us to identify BMP-4 as a potent stimulator of B-cell development in vitro. Further, the analysis suggested that there existed possibilities for progenitor B cells to send signals to

  4. A Rare Case of Waldenström Macroglobulinemia/Lymphoplasmacytic Lymphoma with Light Chain Discrepancy between B Lymphocyte Population and Serum Paraprotein.

    Science.gov (United States)

    Kim, Hyun Jeong; Hur, Mina; Kim, Hanah; Moon, Hee-Won; Yun, Yeo-Min; Kim, Sung Yong; Lee, Mark Hong

    2015-01-01

    Waldenström macroglobulinemia (WM) is a subset of lymphoplasmacytic lymphoma with bone marrow involvement, monotypic immunoglobulin (Ig) M and a light chain of neoplastic cells. A 68-year-old woman presented with fever, nausea, vomiting, and pancytopenia. Her serum albumin/globulin ratio was reversed, and monoclonal gammopathy of IgM, lambda type (23.20%, 1.58 g/dL) was detected. In her bone marrow, increased small lymphocytes were admixed with plasmacytoid lymphocytes and plasma cells. She was diagnosed as having lymphoplasmacytic variant of WM. Immunohistochemical stains and flow cytometic analysis revealed two distinct populations; monoclonal B cells (kappa+) and abnormal plasma cells (CD19-/CD56+/lambda+). She expired 19 days after admission due to septic shock. This is a rare case of WM exhibiting a light chain discrepancy between monoclonal B lymphocytes and paraprotein-secreting plasma cells. Light chain restriction may occur distinctly between lymphocyte and plasma cell populations in WM.

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

    Science.gov (United States)

    Müller, Nike; Schulte, Dominik M; Hillebrand, Susann; Türk, Kathrin; Hampe, Jochen; Schafmayer, Clemens; Brosch, Mario; von Schönfels, Witigo; Ahrens, Markus; Zeuner, Rainald; Schröder, Johann O; Blüher, Matthias; Gutschow, Christian; Freitag-Wolf, Sandra; Stelmach-Mardas, Marta; Saggau, Carina; Schreiber, Stefan; Laudes, Matthias

    2014-01-01

    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 (pr = 0.43, panti-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.

  6. Enlarged colitogenic T cell population paradoxically supports colitis prevention through the B-lymphocyte-dependent peripheral generation of CD4(+)Foxp3(+) Treg cells.

    Science.gov (United States)

    do Canto, Fábio Barrozo; Campos, Sylvia Maria Nicolau; Granato, Alessandra; da Silva, Rafael F; de Paiva, Luciana Souza; Nóbrega, Alberto; Bellio, Maria; Fucs, Rita

    2016-06-29

    Intestinal inflammation can be induced by the reconstitution of T/B cell-deficient mice with low numbers of CD4(+) T lymphocytes depleted of CD25(+)Foxp3(+) regulatory T cells (Treg). Using RAG-knockout mice as recipients of either splenocytes exclusively depleted of CD25(+) cells or FACS-purified CD4(+)CD25(-)Foxp3(-) T cells, we found that the augmentation of potentially colitogenic naïve T cell numbers in the inoculum was unexpectedly beneficial for the suppression of colon disease and maintenance of immune homeostasis. Protection against T cell-mediated colitis correlated with a significant increment in the frequency of peripherally-induced CD4(+)CD25(+)Foxp3(+) T (pTreg) cells, especially in the mesenteric lymph nodes, an effect that required the presence of B cells and CD4(+)CD25(-)Foxp3(+) cells in physiological proportions. Our findings support a model whereby the interplay between B lymphocytes and a diversified naïve T cell repertoire is critical for the generation of CD4(+)CD25(+)Foxp3(+) pTreg cells and colitis suppression.

  7. RUSSIAN EXPERIENCE WITH USING MONOCLONAL ANTIBODIES TO B-LYMPHOCYTES (RITUXIMAB IN SYSTEMIC VASCULITIDES ASSOCIATED WITH NEUTROPHIL CYTOPLASMIC ANTIBODIES (PRELIMINARY RESULTS OF THE RUSSIAN REGISTER NORMA

    Directory of Open Access Journals (Sweden)

    T. V. Beketova

    2014-01-01

    Full Text Available In 2013, Russia registered officially the indications for the use of monoclonal antibodies to B-lymphocytes (rituximab, RTM in systemic vasculitides associated with antineutrophil cytoplasmic antibodies (ANCA-SV. This communication presents the preliminary results of the Russian register of the RTM application in autoimmune diseases (NORMA that has included 50 patients with ANCA-SV treated in 14 cities of the Russian Federation. Twenty-five of 50 (50% patients received repeated courses of RTM. RTM has demonstrated a high efficacy and a good profile of treatment safety in patients with ANCA-SV in real-life national clinical practice. Among 25 patients who had been followed up for over 12 months, the remission was achieved in 92% of cases, a decrease in the ANCA-SV activity was observed in 8%. The efficacy of RTM increased when performing repeated courses, while it has been noted that the positive results can be obtained by prescribing a repeated course of RTM at a reduced dose (500–1000 mg. Prescription of the repeated courses was primarily required in patients with granulomatosis and polyangiitis affecting the lungs. Care should be taken when combining RTM treatment with cytostatics (primarily with cyclophosphamide because of the risk of secondary immunodeficiency and infectious adverse events (AE, which have been the most frequent serious AE (12% in patients with ANCA-SV.

  8. Costimulation of resting B lymphocytes alters the IL-4-activated IRS2 signaling pathway in a STAT6 independent manner: implications for cell survival and proliferation

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    IL-4 is an important B cell survival and growth factor.IL-4 induced the tyrosine phosphorylation of IRS2 in resting B lymphocytes and in LPS- or CD40L-activated blasts.Phosphorylated IRS2 coprecipitated with the p85 subunit of PI 3' kinase in both resting and activated cells.By contrast,association of phosphorylated IRS2 with GRB2 was not detected in resting B cells after IL-4 treatment although both proteins were expressed.However,IL-4 induced association of IRS2 with GRB2 in B cell blasts.The pattern of IL-4-induced recruitment of p85 and GRB2 to IRS2 observed in B cells derived from STAT6 null mice was identical to that observed for normal mice.While IL-4 alone does not induce activation of MEK,a MEK1 inhibitor suppressed the IL-4-induced proliferative response of LPS-activated B cell blasts.These results demonstrate that costimulation of splenic B cells alters IL-4-induced signal transduction independent of STAT6 leading to proliferation.Furthermore,proliferation induced by IL-4 in LPS-activated blasts is dependent upon the MAP kinase pathway.

  9. B淋巴细胞刺激因子对慢性特发性荨麻疹患者产生抗FcεRI抗体和抗IgE抗体的影响%Influence of B lymphocyte stimulator on the production of anti-FcεRI and anti-IgE antibodies by B lymphocytes from patients with chronic idiopathic urticaria

    Institute of Scientific and Technical Information of China (English)

    康尔恂; 李杰; 孙丽伟; 韩春玉; 闫丽萍; 杨建

    2013-01-01

    目的 探讨B淋巴细胞刺激因子(BlyS)能否刺激慢性特发性荨麻疹(CIU)患者B淋巴细胞产生抗FcεRI抗体或抗IgE抗体.方法 设CIU患者组和健康对照组.ELISA法测定血清中BlyS、抗FcεRI抗体和抗IgE抗体水平,分离培养受试者外周血B淋巴细胞,在培养液中加入BlyS,检测培养液中抗FcεRI抗体和抗IgE抗体水平,分析BlyS与抗FcεRI抗体和抗IgE抗体产生的相关性.结果 CIU患者血清BlyS水平显著高于健康对照组(t=3.04,P< 0.01),抗FcεRI抗体和抗IgE抗体水平均显著高于健康对照组(t=3.51,P<0.01;t=3.29,P< 0.01).CIU患者血清中抗FcεRI抗体和抗IgE抗体水平与BlyS水平呈正相关(r=0.93,P<0.01;r=0.91,P< 0.01);CIU患者外周血B淋巴细胞培养液中加入有效浓度BlyS后,B淋巴细胞培养液中抗FcεRI抗体和抗IgE抗体水平均显著高于不加BlyS的空白对照(t=3.67,P< 0.01;t=3.56,P< 0.01),2种抗体在培养液中的水平与BlyS浓度呈正相关(r=0.96,P< 0.01;r=0.91,P< 0.01);抗FcεRI抗体和抗IgE抗体在CIU患者血清与培养液中的检出符合率分别为94.76%和87.84%.结论 CIU患者血液中BlyS水平增高可刺激B淋巴细胞产生抗FcεRI抗体或抗IgE抗体,可能与CIU发病有关.%Objective To explore if B lymphocyte stimulator (BlyS) stimulates B lymphocytes from patients with chronic idiopathic urticaria (CIU) to produce anti-high affinity IgE receptor (FcεRI) or anti-IgE antibodies.Methods Totally,300 CIU patients and 300 health controls were enrolled in this study.Blood samples were obtained from these subjects.Peripheral blood B lymphocytes were isolated and cultured in vitro for 72 hours.Then,BlyS of various concentrations (2,4,8,16 ng/ml) was added to the culture medium of B lymphocytes followed by another 72-hour culture.Enzyme-linked immunosorbent assay was performed to determine the serum levels of BlyS,anti-FcεRI and anti-IgE antibodies,as well as the supernatant levels of anti

  10. 一个自闭症家系的B淋巴细胞周期研究%Altered Cell Cycle of B Lymphocytes from an Autistic Family

    Institute of Scientific and Technical Information of China (English)

    申晨; 邹小兵; 邹俊华; 申阿东; 钟南

    2012-01-01

    目的 了解自闭症儿童的B淋巴细胞的细胞周期是否存在变异,为寻找自闭症的生物标志物并进一步为揭示自闭症的发病机制奠定基础.方法 运用B淋巴细胞建系、淋巴细胞培养、细胞周期检测以及统计学分析的方法,对一个汉族自闭症家系进行研究.该家系由父母及6个子女组成,父母表现型正常,而其中3名子女为自闭症患儿,3名为非自闭症儿童.结果 分析显示,B淋巴细胞的细胞周期在自闭症儿童组(相对于非自闭症儿童组)出现了S期细胞比例的增加和G0/G1期细胞比例的减少,同时代表增殖能力的“S期+G2/M期”的细胞比例也出现显著增加.结论 细胞周期的变化依赖于细胞内调控机制的改变,可能涉及到多种细胞周期蛋白的表达和调控变化,自闭症患儿存在B淋巴细胞细胞周期变异这一现象为进一步揭示自闭症的发病机制提供了线索.此外,如果本研究结果能够在大样本中得到肯定,则可作为自闭症的生物标志物用于疾病辅助诊断而具有良好的临床应用价值.%Objective To discover whether the cell cycle of B lymphocyte from autistic children were different from inartistic children. Methods One family including parents, three autistic children and three non-autistic children was involved in this study. The B lymphoblastoma cell construction, cell culture and cell cycle detection by flow cytometry (FCM) were carried out. Results FCM analysis showed that the percentage of G0/G1 phase cells decreased but that of S phase cells increased in autistic children compared with non-autistic siblings. The cell percentage of "S +G2/M" phase which represents cell proliferation also increased significantly in autistic children. Conclusion Alteration of cell cycle is the result of the intracellular regulating, which may involve variety changes of protein expression and regulation. The phenomenon that autistic children had alerted B lymphocyte cell

  11. 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.

    Science.gov (United States)

    Liphaus, Bernadete L; Kiss, Maria H B; Carrasco, Solange; Goldenstein-Schainberg, Claudia

    2006-01-01

    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.

  12. Circulating human B and plasma cells. Age-associated changes in counts and detailed characterization of circulating normal CD138- and CD138+ plasma cells. : Blood B-lymphocytes and plasma cells in adults

    OpenAIRE

    2010-01-01

    International audience; Generation of B and plasma cells involves several organs with a necessary cell trafficking between them. A detailed phenotypic characterization of four circulating B-cell subsets (immature-, naïve-, memory- B-lymphocytes and plasma cells) of 106 healthy adults was realized by multiparametric flow cytometry. We show that CD10, CD27 and CD38 is the minimal combination of subsetting markers allowing unequivocal identification of immature (CD10(+)CD27(-)CD38(+), 6+/-6 cell...

  13. 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.

  14. Differential expression of adhesion molecules and chemokines between nasal and small intestinal mucosae: implications for T- and sIgA+ B-lymphocyte recruitment.

    Science.gov (United States)

    Bourges, Dorothée; Chevaleyre, Claire; Wang, CaiHong; Berri, Mustapha; Zhang, XiaoMei; Nicaise, Laetitia; Meurens, François; Salmon, Henri

    2007-12-01

    Nasal and small intestinal mucosae are the first sites of contact with infectious agents and the sites of T-cell-mediated and secreted immunoglobulin A (IgA)-mediated defences against pathogens. We investigated the factors controlling the infiltration of CD3(+) T lymphocytes and surface IgA(+) (sIgA(+)) B lymphocytes into swine epithelium and lamina propria (LP) within and between these two mucosal effector sites. Vascular addressins, vascular cell adhesion molecule 1 and mucosal addressin cell adhesion molecule-1 were reciprocally expressed in both mucosae. Strong expression of alpha(4)beta(1) relative to alpha(4)beta(7) was characteristic of CD3(+) T cells in nasal mucosa LP and epithelium and of sIgA(+) cells in nasal mucosa epithelium. The same profile was observed on corresponding blood cells. Conversely, higher levels of integrins beta(7) and alpha(4)beta(7) than alpha(4)beta(1) were characteristic of CD3(+) T cells and sIgA(+) cells in the small intestine. However, about 40% of the LP-activated sIgA(+) cells displayed sIgA(high), integrin alpha(4) and integrin alpha(4) expression. Whereas CCL19, CXCL12, CCL21 and CCL28 messenger RNAs were similarly expressed in both mucosae, CCL25 messenger RNA was only expressed in the small intestine. Thus, the nasal and small intestine mucosae represent separate compartments for infiltration by CD3(+) T cells and sIgA(+) effector cells, with the exception of a population of small intestine activated sIgA(+) cells, which may gain access to both mucosae.

  15. Reactivation of persistent Epstein-Barr virus (EBV) causes secretion of thyrotropin receptor antibodies (TRAbs) in EBV-infected B lymphocytes with TRAbs on their surface.

    Science.gov (United States)

    Nagata, Keiko; Nakayama, Yuji; Higaki, Katsumi; Ochi, Marika; Kanai, Kyosuke; Matsushita, Michiko; Kuwamoto, Satoshi; Kato, Masako; Murakami, Ichiro; Iwasaki, Takeshi; Nanba, Eiji; Kimura, Hiroshi; Hayashi, Kazuhiko

    2015-01-01

    Epstein-Barr virus (EBV) is a ubiquitous virus that infects most adults latently. It persists in B lymphocytes and reactivates occasionally. Graves' disease is an autoimmune hyperthyroidism caused by thyrotropin receptor antibodies (TRAbs). We have reported that Graves' disease patients and healthy controls have EBV-infected lymphocytes that have TRAbs on their surface (TRAb(+)EBV(+) cells) in peripheral blood mononuclear cells (PBMCs). EBV reactivation is known to be associated with plasma cell differentiation and antibody production of B cells. In this study, we investigated whether TRAb(+)EBV(+) cells really produce TRAbs or not when persistent EBV is reactivated. We cultured PBMCs from 12 Graves' disease patients and 12 healthy controls for several days with cyclosporine A to expand the EBV-infected cell population, and then compared TRAb levels between EBV reactivation by 33 °C culture and EBV nonreactivation by 37 °C culture of PBMCs. Flow cytometry confirmed that all samples at day 0 (reactivation starting point) contained TRAb(+)EBV(+) cells. During 33 °C culture, EBV-reactivated cells with EBV-gp350/220 expression increased from about 1 to 4%. We quantified TRAb levels in culture fluids by radio-receptor assay, and detected an increased concentration for at least one sampling point at 33 °C (from days 0 to 12) for all patients and healthy controls. TRAb levels were significantly higher in supernatants of 33 °C culture than of 37 °C culture, and also significantly higher in supernatants from patients than those from controls. This study revealed TRAb production from TRAb(+)EBV(+) cells in response to reactivation induction of persistent EBV in different efficiencies between patients and controls.

  16. Analysis of Ig V{sub H} region genes encoding IgE antibodies in splenic B lymphocytes of a patient with asthma

    Energy Technology Data Exchange (ETDEWEB)

    Snow, R.E.; Chapman, C.J.; Stevenson, F.K. [Southampton Univ. Hospitals (United Kingdom)] [and others

    1995-05-15

    An atopic patient with hypersensitivity against house dust mite died as a result of an asthmatic attack. A portion of the spleen was obtained and was used to analyze the spectrum of Ig heavy chain V regions involved in encoding IgE Abs. A nested PCR technique generated 14 cloned V{sub H} sequences that had distinct CDR3 regions; 5 of 14 were derived from the minor V{sub H}5 family, and the remainder derived from the larger families, V{sub H}3 (6 of 14) and V{sub H}4 (3 of 14). One of the V{sub H}3-derived sequences was present as a repeated sequence in three clones. A control PCR with the same V{sub H} primers in combination with J{sub H} primers yielded only 1 of 13 sequences from V{sub H}5, indicating preferential V{sub H}5 usage only for IgE. Analysis of V{sub H}5-C{epsilon} sequences revealed usage of a single gene, DP73, with extensive mutations and several {open_quotes}hot spots{close_quotes} containing common replacement amino acids. However, there was no concentration of replacement mutations in the CDRs, which conventionally would indicate a role for Ag selection. The V{sub H}3 and V{sub H}4 genes in combination with C{epsilon} also harbored extensive somatic mutations. From these findings in splenic B lymphocytes, and those of a previous study of blood lymphocytes, it seems that preferential usage of V{sub H}5 genes and extensive somatic hypermutation are characteristic of B cells synthesizing IgE in patients with allergic disease. 27 refs., 3 figs., 2 tabs.

  17. Monoclonal B lymphocytes with the characteristics of "indolent" chronic lymphocytic leukemia are present in 3.5% of adults with normal blood counts.

    Science.gov (United States)

    Rawstron, Andy C; Green, Michael J; Kuzmicki, Anita; Kennedy, Ben; Fenton, James A L; Evans, Paul A S; O'Connor, Sheila J M; Richards, Stephen J; Morgan, Gareth J; Jack, Andrew S; Hillmen, Peter

    2002-07-15

    Molecular and cellular markers associated with malignant disease are frequently identified in healthy individuals. The relationship between these markers and clinical disease is not clear, except where a neoplastic cell population can be identified as in myeloma/monoclonal gammopathies of undetermined significance (MGUS). We have used the distinctive phenotype of chronic lymphocytic leukemia (CLL) cells to determine whether low levels of these cells can be identified in individuals with normal complete blood counts. CLL cells were identified by 4-color flow cytometric analysis of CD19/CD5/CD79b/CD20 expression in 910 outpatients over 40 years old. These outpatients were age- and sex-matched to the general population with normal hematologic parameters and no evident history of malignant disease. CLL phenotype cells were detectable in 3.5% of individuals at low level (median, 0.013; range, 0.002- 1.458 x 10(9) cells/L), and represented a minority of B lymphocytes (median, 11%; range, 3%-95%). Monoclonality was demonstrated by immunoglobulin light-chain restriction in all cases with CLL phenotype cells present and confirmed in a subset of cases by consensus-primer IgH-polymerase chain reaction. As in clinical disease, CLL phenotype cells were detected with a higher frequency in men (male-to-female ratio, 1.9:1) and elderly individuals (2.1% of 40- to 59-year-olds versus 5.0% of 60- to 89-year-olds, P =.01). The neoplastic cells were identical to good-prognosis CLL, being CD5+23+20(wk)79b(wk)11a(-)22(wk)sIg(wk)CD38-, and where assessed had a high degree (4.8%-6.6%) of IgH somatic hypermutation. The monoclonal CLL phenotype cells present in otherwise healthy individuals may represent a very early stage of indolent CLL and should be useful in elucidating the mechanisms of leukemogenesis.

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

    Directory of Open Access Journals (Sweden)

    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.

  19. B lymphocytes in neuromyelitis optica.

    Science.gov (United States)

    Bennett, Jeffrey L; O'Connor, Kevin C; Bar-Or, Amit; Zamvil, Scott S; Hemmer, Bernhard; Tedder, Thomas F; von Büdingen, H-Christian; Stuve, Olaf; Yeaman, Michael R; Smith, Terry J; Stadelmann, Christine

    2015-06-01

    Neuromyelitis optica (NMO) is an inflammatory autoimmune disorder of the CNS that predominantly affects the spinal cord and optic nerves. A majority (approximately 75%) of patients with NMO are seropositive for autoantibodies against the astrocyte water channel aquaporin-4 (AQP4). These autoantibodies are predominantly IgG1, and considerable evidence supports their pathogenicity, presumably by binding to AQP4 on CNS astrocytes, resulting in astrocyte injury and inflammation. Convergent clinical and laboratory-based investigations have indicated that B cells play a fundamental role in NMO immunopathology. Multiple mechanisms have been hypothesized: AQP4 autoantibody production, enhanced proinflammatory B cell and plasmablast activity, aberrant B cell tolerance checkpoints, diminished B cell regulatory function, and loss of B cell anergy. Accordingly, many current off-label therapies for NMO deplete B cells or modulate their activity. Understanding the role and mechanisms whereby B cells contribute to initiation, maintenance, and propagation of disease activity is important to advancing our understanding of NMO pathogenesis and developing effective disease-specific therapies.

  20. B lymphocyte differentiation in lethally irradiated and reconstituted mice. I. The effect of strontium-89 induced bone marrow aplasia on the recovery of the B cell compartment in the spleen

    Energy Technology Data Exchange (ETDEWEB)

    Rozing, J.; Buurman, W.A.; Benner, R.

    1976-06-01

    The influence of /sup 89/Sr-treatment on the recovery of the B cell compartment in lethally irradiated, fetal liver reconstituted mice was studied by means of membrane fluorescence, /sup 89/Sr is a bone-seeking radio-isotope which causes in a dose of 3 ..mu..Ci /sup 89/Sr/g body weight a depletion of all nucleated cells, including immunoglobulin-bearing (B) cells, of the bone marrow. Treatment of irradiated and fetal liver reconstituted mice with 3 ..mu..Ci /sup 89/Sr/g body weight immediately and at 17 days after irradiation and reconstitution prevented recovery of the nucleated cell population, including B cells, in the bone marrow. In the spleen of such mice both nucleated cells and B cells reappeared at day 7 and 14 respectively. The B cell population in the spleen did not recover up to normal values during the experimental period of 45 days. It is concluded that B cell differentiation in lethally irradiated, fetal liver reconstituted mice can take place outside the bone marrow. The efficiency of this extra-medullary differentiation is discussed. The conclusion was drawn that mice with a /sup 89/Sr-induced bone marrow aplasia are able to generate B lymphocytes. Consequently the bone marrow microenvironment seems not to be obligate to the differentiation of B lymphocytes. The peripheral lymphoid organs of such mice were found to be unable to compensate completely for the absence of B lymphocyte production in the bone marrow.

  1. 骨髓间充质干细胞对异体外周血B淋巴细胞的免疫调节作用%The immunoregulatory effects of bone marrow mesenchymal stem cells on allogeneic peripheral B lymphocyte

    Institute of Scientific and Technical Information of China (English)

    武令启; 白海; 王存邦; 杨小亮; 赵强; 杨义武; 林梅

    2008-01-01

    Objective To study the immunoregulatory effects of bone marrow mesenchymal stem cells (MSC) on allogeneic peripheral B lymphocytes in vitro. Methods MSCs were isolated and cultured from bone marrow by gradient centrifugation. Mononuclear cells were isolated routinely from peripheral blood, then monocytes were eliminated by L-leucine methy ester method. Remained T lymphocytes were eliminated by AET-SRBC rosette method. The action of MSCs and its supernatant on B lymphocytes proliferation in the presence of anti-human IgM goat antibodies (anti-IgM) was investigated by MTT. The IgG, IgM in the supernatant were detected by ELISA. The percent of apoptosis B lymphocytes, co-cultured with MSCs for 24 or 48h, was assayed by FACS. Results MSCs and its supernatant inhibited B lymphocytes proliferation and Ig secretion. The inhibitory effect depended on the amount of MSCs and condition of its supernatant. The date of FACS indicated that the apoptosis ratio of B lymphocytes, co-cultured with MSCs for different times, were non-significant. The inhibitory effect of MSCs on B lymphocytes was temporary and reversible. Conclusion MSCs have immunoregulatory effects on B lymphocytes, and its mechanisms are complex, not only correlating with the concentration of MSCs but also the action between cells and the secretory cytokine of MSCs.%目的 探讨骨髓间充质干细胞(mesenchymal stem cells, MSC)在体外对异体外周血B淋巴细胞的免疫调节作用.方法 用密度梯度离心法从骨髓中分离、培养MSC,从外周血中分离单个核细胞,L-亮氨酸甲酯去除单核细胞,以2-氨乙基硫脲溴化物(AET)处理绵羊红细胞(SRBC)的花环形成法,去除T淋巴细胞获得纯化的B淋巴细胞.用羊抗人IgM单克隆抗体(anti-IgM)刺激与或未与MSC或其培养上清共培养3d的B淋巴细胞,应用MTT法测8淋巴细胞的增殖,ELISA法测培养上清中免疫球蛋白IgG、lgM的产生,应用流式细胞术分别检测与MSC共培养24、48h

  2. Aged B lymphocytes retain their ability to express surface markers but are dysfunctional in their proliferative capability during early activation events

    Directory of Open Access Journals (Sweden)

    McGlauchlen Kiley

    2008-11-01

    Full Text Available Abstract Background Ageing is associated with dysfunction in the humoral response leading to decreased protection against infectious diseases. Defects in T cell function due to age have been well characterized but it is unclear if dysfunctions in antibody responses are due to deficiencies in a helper environment or intrinsic B cell defects. Previous studies from our laboratory have shown that aged B lymphocytes are able to differentiate into high affinity antibody-secreting cells at a frequency similar to their young counterparts. However, expansion of B cells in vivo was reduced in aged animals when compared to young. Methods To further investigate the cause of this reduced expansion, we have now examined early activation events of aged B cells in response to anti-CD40 monoclonal antibody (mAb and lipopolysaccharide (LPS stimulation in vitro. To do this spleen cells were harvested from young, middle-aged and aged quasi-monoclonal (QM mice and cultured in complete RPMI for 24 and 48 hours. Cultures contained either LPS or anti-CD40 mAb and murine IL-4. Cells were collected and analyzed using flow cytometry. To examine the proliferative capacity of aged B cells spleen cells were collected as before and cultured in 96 well microtiter plates with either LPS or anti-CD40 mAb and murine IL-4 for 24 hours. Tritiated thymidine ([3H]-Tdr was added to each well and incubated for another 24 hours after which cells were collected and analyzed using a scintillation counter. Results Resting aged B cells exhibited similar levels of CD40 expression when compared to young cells and efficiently up-regulated CD86 and CD69 and also down-regulated CD38 upon stimulation. However, aged B cells proliferated less than young B cells and showed a consistent, but not statistically significant, reduction in their ability to form blast cells. Conclusion Aged B cells exhibited a reduced response in some early activation events but produced at least a partial response in all

  3. HIV感染者中B细胞免疫应答的研究进展%Progress of B lymphocyte responses among HIV-infected individuals

    Institute of Scientific and Technical Information of China (English)

    王万海; 徐建青; 张晓燕

    2011-01-01

    HIV disease is associated with abnormalities in all major lymphocyte populations, including B cells, which ultimately results in severe exhaustion of several lymphocyte functions and increased susceptibility to secondary and opportunistic infections. Among these cells, B lymphocytes are severely damaged and show signs of phenotypic and functional alterations. In parallel to the polyclonal B cell activation and hypergammaglobulinemia,B cells from patients show impaired reactivity to immunisation and poorly inducible antibody responses. Thus, a better understanding of the pathogenic mechanisms of B-cell abnormalities in HIV disease can potentially lead to new strategies for improving antibody responses against opportunistic pathogens that afflict HIV-infected individuals and against HIV itself, in the context of both HIV infection and an antibody-based HIV vaccine.%HIV感染引起了免疫系统慢性持续的活化而造成免疫细胞哑群的异常及其功能的耗竭(包括B淋巴细胞),使得宿主二次感染和机会性感染的易感性增加.B细胞的异常不仅出现在其表型及亚群上,更体现在功能的改变.伴随着B细胞的多克隆活化和高免疫球蛋白血症的出现,B细胞还表现出了对外源抗原无反应性及产生抗体的异常等功能缺陷方面的特征.对此,深入了解HIV感染过程中B细胞异常的致病机制,以期为今后通过改善HIV患者的体液反应来预防其机会感染的发生并为以抗体为基础的HIV疫苗研究策略提供有益的参考.

  4. DNA from protozoan parasites Babesia bovis, Trypanosoma cruzi, and T. brucei is mitogenic for B lymphocytes and stimulates macrophage expression of interleukin-12, tumor necrosis factor alpha, and nitric oxide.

    Science.gov (United States)

    Shoda, L K; Kegerreis, K A; Suarez, C E; Roditi, I; Corral, R S; Bertot, G M; Norimine, J; Brown, W C

    2001-04-01

    The activation of innate immune responses by genomic DNA from bacteria and several nonvertebrate organisms represents a novel mechanism of pathogen recognition. We recently demonstrated the CpG-dependent mitogenic activity of DNA from the protozoan parasite Babesia bovis for bovine B lymphocytes (W. C. Brown, D. M. Estes, S. E. Chantler, K. A. Kegerreis, and C. E. Suarez, Infect. Immun. 66:5423-5432, 1998). However, activation of macrophages by DNA from protozoan parasites has not been demonstrated. The present study was therefore conducted to determine whether DNA from the protozan parasites B. bovis, Trypanosoma cruzi, and T. brucei activates macrophages to secrete inflammatory mediators associated with protective immunity. DNA from Escherichia coli and all three parasites stimulated B-lymphocyte proliferation and increased macrophage production of interleukin-12 (IL-12), tumor necrosis factor alpha (TNF-alpha), and nitric oxide (NO). Regulation of IL-12 and NO production occurred at the level of transcription. The amounts of IL-12, TNF-alpha, and NO induced by E. coli and protozoal DNA were strongly correlated (r2 > 0.9) with the frequency of CG dinucleotides in the genome, and immunostimulation by DNA occurred in the order E. coli > or = T. cruzi > T. brucei > B. bovis. Induction of inflammatory mediators by E. coli, T. brucei, and B. bovis DNA was dependent on the presence of unmethylated CpG dinucleotides. However, at high concentrations, E. coli and T. cruzi DNA-mediated macrophage activation was not inhibited following methylation. The recognition of protozoal DNA by B lymphocytes and macrophages may provide an important innate defense mechanism to control parasite replication and promote persistent infection.

  5. HCV infection and morphologic study in B lymphocytes of patient with hepatitis C%丙型肝炎病毒对人B淋巴细胞系的感染及其形态学研究

    Institute of Scientific and Technical Information of China (English)

    姚鹏; 陈良标; 胡学玲; 陈佩兰; 胡大荣

    2001-01-01

    目的 研究HCV对人B淋巴细胞的感染,建立HCV感染的丙型肝炎患者B淋巴细胞模型(CBCL),并进行HCV的形态学研究。方法用EB病毒转化B细胞建立B细胞系,以逆转录多聚酶链反应(RT-PCR)、免疫组织化学、原位杂交方法检测B细胞系上清液及细胞内的HCV抗原及HCV RNA,并通过电镜对HCV进行形态学研究。结果细胞系上清液中HCV RNA呈阳性,细胞内HCV抗原及HCV RNA均呈阳性,电镜观察结果发现细胞内存在65nm和110nm圆球型病毒颗粒,并可见病毒芽生形成现象。结论 HCV可感染人B细胞并在其中复制。病毒在感染细胞胞质空泡部位合成和组装,以芽生方式进入胞质空泡内形成病毒颗粒。%Objective To study HCV infection in B lymphocytes of patients with hepatitis C and to establish a B cell line with HCV infection and observe the hepatitis C virus like particles. Methods A B lymphoblastoid cell line was established by Epstein-Barr virus induced transformation directly from peripheral blood mononuclecyte cells of a patient with hepatitis C. The HCV antigen and HCV RNA were detected by immunohistochemical technique. Reverse transcription-polymerase chain reaction(RT-PCR) and in situ hybridization and HCV particle were detected by electron microscopy. Results Positive HCV RNA was found in supernatants of B cell line. HCV Ag and HCV RNA were also showed positive. Electron microscopy observed HCV spherical virus like particles with a diameter of approximately 65 nm and 110nm and the "bud mutation"of HCV in the cytoplasmic vesicles of B lymphocytes. Conclusion HCV could infect B lymphocytes and replicate in the cell line. HCV particles are formed by "bud mutation" of HCV in the cytoplasmic vesicles of B-lymphocytes.

  6. Enhanced immunogenicity of pneumococcal surface adhesin A (PsaA in mice via fusion to recombinant human B lymphocyte stimulator (BLyS

    Directory of Open Access Journals (Sweden)

    Mambula Salamatu S

    2011-02-01

    Full Text Available Abstract Background B lymphocyte stimulator (BLyS is a member of the tumor necrosis factor superfamily of ligands that mediates its action through three known receptors. BLyS has been shown to enhance the production of antibodies against heterologous antigens when present at elevated concentrations, supporting an immunostimulatory role for BLyS in vivo. Methods We constructed a fusion protein consisting of human BLyS and Pneumococcal Surface Adhesin A (PsaA and used this molecule to immunize mice. The immunostimulatory attributes mediated by BLyS in vivo were evaluated by characterizing immune responses directed against PsaA. Results The PsaA-BLyS fusion protein was able to act as a co-stimulant for murine spleen cell proliferation induced with F(ab'2 fragments of anti-IgM in vitro in a fashion similar to recombinant BLyS, and immunization of mice with the PsaA-BLyS fusion protein resulted in dramatically elevated serum antibodies specific for PsaA. Mice immunized with PsaA admixed with recombinant BLyS exhibited only modest elevations in PsaA-specific responses following two immunizations, while mice immunized twice with PsaA alone exhibited undetectable PsaA-specific serum antibody responses. Sera obtained from PsaA-BLyS immunized mice exhibited high titers of IgG1, IgG2a, IgG2b, and IgG3, but no IgA, while mice immunized with PsaA admixed with BLyS exhibited only elevated titers of IgG1 following two immunizations. Splenocytes from PsaA-BLyS immunized mice exhibited elevated levels of secretion of IL-2, IL-4 and IL-5, and a very modest but consistent elevation of IFN-γ following in vitro stimulation with PsaA. In contrast, mice immunized with either PsaA admixed with BLyS or PsaA alone exhibited modestly elevated to absent PsaA-specific recall responses for the same cytokines. Mice deficient for one of the three receptors for BLyS designated Transmembrane activator, calcium modulator, and cyclophilin ligand [CAML] interactor (TACI exhibited

  7. A study of T CD4, CD8 and B lymphocytes in narcoleptic patients Estudo dos linfócitos T CD4, CD8 e B em pacientes com narcolepsia

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    Fernando Morgadinho Santos Coelho

    2007-06-01

    Full Text Available Narcolepsy is characterized by excessive daytime sleep and cataplexy. Little is known about the possible difference in pathophysiology between patients with or without cataplexy. OBJECTIVE: To quantify T CD4, T CD8 and B lymphocytes in subgroups of patients with narcolepsy and the presence or absence of the HLA-DQB1*0602 allele between groups. METHOD: Our study was prospective and controlled (transversal with 22 narcoleptic patients and 23 health control subjects. Patients underwent an all-night polysomnographic recording (PSG and a multiple sleep latency Test (MSLT. The histocompatibility antigen allele (HLA-DQB1*0602, T CD4, CD8 and B lymphocytes were quantified in control subjects and in narcoleptics. RESULTS: The HLA-DQB1*0602 allele was identified in 10 (62.5% of our 16 cataplexic subjects and in 2 (33.3% of the 6 patients without cataplexy (p=0.24. In control subjects, HLA-DQB1*0602 allele was identified in 5 (20%. A significant decrease in T CD4 and B lymphocytes was found in narcoleptic patients with recurrent cataplexy when compared with our patients without cataplexy. CONCLUSION: Autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis were associated with a decrease in sub-group of T CD4 and B lymphocytes. A drop in B lymphocytes count in reumathoid arthritis might, it is posited, be correlated to the presence of HLA-DRB1 allele along with an overall worsened outcome of the affliction. The theory of an increase in consumption of B lymphocytes over the maturation phase has likewise been put forward. Our study reinforces the view that narcolepsy should be considered from an immunological perspective.A narcolepsia é caracterizada por sonolência excessiva diurna e cataplexia. Pouco se sabe sobre as diferenças fisiopatológicas entre pacientes com e sem cataplexia. OBJETIVO: Quantificar os linfócitos T CD4, T CD8 e B e a presença do alelo HLA-DQB1*0602 nos subgrupos de pacientes com narcolepsia. MÉTODO: O

  8. Expression of B lymphocyte activating factor in decidual and chorionic membranes of women with early spontaneous abortion and its significance%胚胎停育患者蜕膜和绒毛组织中B淋巴细胞刺激因子的表达及意义

    Institute of Scientific and Technical Information of China (English)

    高艳萍; 郝冬梅

    2011-01-01

    目的 探讨胚胎停育患者蜕膜和绒毛组织中B淋巴细胞刺激因子(BAFF)的表达与胚胎停育的关系.方法 随机选择早孕胚胎停育患者30例作为实验组,正常早孕人工流产者30例为对照组.用免疫组化(二步法)法测定蜕膜及绒毛中BAFF的表达情况.结果 BAFF在所有标本中都有表达,但胚胎停育组蜕膜中BAFF的表达均低于对照组(P<0.05),胚胎停育组蜕膜血管内皮中则无表达.结论 BAFF与胚胎停育有一定的关联,可能是导致胚胎停育的原因之一.%Objective To study the correlation between the expression of B lymphocyte activating factor in decidual and chorionic membranes and early spontaneous abortion. Methods Thirty women with early spontaneous abortion served as an experimental group and 30 women who had artificial abortion for normal early pregnancy served as a control group. Expression of B lymphocyte activating factor in decidual and chorionic membranes was detected by immunohistochemistry. Results B lymphocyte activating factor was expressed in all samples of decidual and chorionic membranes. However, its expression level in decidual membrane was lower in experimental group than in control group(P<0.05). B lymphocyte activating factor was not expressed in angioendothelium of experimental group. Conclusion B lymphocyte activating factor is associated with early spontaneous abortion and may be one of the reasons for early spontaneous abortion.

  9. 小儿特发性血小板减少性紫癜外周血T、B淋巴细胞观察%The observation of T and B lymphocyte in peripheral of infantile idiopathic thrombocytopenic purpura

    Institute of Scientific and Technical Information of China (English)

    白文杰; 翟凤兰

    2000-01-01

    Objective: To detect the ratio changes of subgroup T lymphocyte and B lymphocyte in infants with ITP. Methods:Manufacturing single nucleus cell with lymphocyte, separate liquid, adding antibody after thermal cultivation and calculatingthe percentage of positive cells using inmuno-fluorescence method. Results: There are no statistie differences between the ITPpatients' T3、T4 and the healthy contral' s there are statistie differences between the ITP patients' T8、 B groups and the healthycontral' s. Conclusion: The patients of infantile ITP may have humoral and cellular immunity factional disorder.%目的:检测ITP患儿T淋巴细胞亚群及B细胞的比值变化。方法:采用荧光免疫法用淋巴细胞分离液配制单个细胞,温育后加入抗体,计算阳性百分率。结果:患儿组T3、T4与健康组差异不显著,T8及B细胞患儿组与健康组差异有显著性。结论:ITP患儿可出现细胞免疫及体液免疫功能紊乱。

  10. HIV/AIDS患者外周血B细胞数量以及TLR9 mRNA表达水平的研究%B lymphocyte counts and Toil-like receptor 9 mRNA expression on cell from HIV-1 infected patients

    Institute of Scientific and Technical Information of China (English)

    孙宏; 姜拥军; 尚红; 耿文清; 崔华露; 赵敏; 韩晓旭; 张子宁; 刘静; 代娣; 王亚男

    2010-01-01

    目的 探讨HIV-1感染后外周血B细胞数量的变化,以及B细胞TLR9 mRNA表达水平与HIV-1感染疾病进展的关系.方法 采集HIV/AIDS患者EDTA抗凝静脉血,荧光抗体染色后用流式细胞仪检测HIV/AIDS患者B细胞数量.密度梯度离心法分离外周血单个核细胞,应用MACS磁珠分选系统分选CD19+B细胞,并采用荧光定量实时PCR技术检测B细胞TLR9 mRNA水平.结果 HIV/AIDS患者B细胞数量显著低于健康对照组(P<0.01),与CD4+T细胞数量呈正相关(r=0.534,P=0.006).HIV/AIDS患者外周血B细胞TIR9 mRNA的表达明显低于健康对照组(P=0.023),与CD4+T细胞数量呈正相关(r=0.390,P=0.040).结论 HIV感染可降低HIV/AIDS患者外周血B细胞数量以及B细胞TLR9 mRNA的表达量,B细胞数量和B细胞TLR9 mRNA的表达量均可能与疾病进展相关.%Objective To study the B lymphocytes counts and the expression of TLR9 mRNA on B lymphocytes in peripheral blood from Chinese HIV-infected patients.Methods The cells from peripheral blood were stained with antibodies labeled with fluorescence and B lymphocytes were counted with flow cytometry.Using the method of magnetic activated cell sorting and real-time PCR,the expression of TLR9 mRNA was measured.Results The B lymphocytes counts in HIV/AIDS patients was significantly lower than that of healthy controls(P <0.01).The B lymphocytes counts in HIV/AIDS patients positively correlated with the CD4 +T cells counts(r =0.534,P = 0.006).The expression of TLR9 mRNA on B lymphocytes in HIV/AIDS patients was significantly lower than that of healthy controls(P =0.023),and positively correlated with the CD4 + T cells counts(r = 0.390,P = 0.040).Conclusion The B lymphocytes counts and the expression of TLR9 mRNA on B lymphocytes in Chinese HIV/AIDS patients were decreased due to HIV infection,which may correlate with disease progression.

  11. 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.

  12. 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.

  13. T、B淋巴细胞功能对流行性牛白血病发生发展的影响%The Relationship Between the Function of T、B Lymphocytes and the Pathogenesis of Enzootic Bovine Leukosis

    Institute of Scientific and Technical Information of China (English)

    王选年; 潘耀谦; 康晓迪; 张改平

    2001-01-01

    本文回顾了T、B淋巴细胞功能与牛白血病发生发展的相关性。阐明了感染BLV牛B细胞淋巴瘤细胞除了来源于B1a(CD5+CD11b+)细胞,也可来源于B1b(CD5- CD11b+)及常规B2(CD5 -CD11b-)细胞。探讨了T细胞功能对牛白血病的发生发展的影响,指出IL-1 2表达下降和IL -10表达增加可能导致了B细胞淋巴肉瘤的形成,Ⅰ型和Ⅱ型细胞因子的不平衡引起了BLV的发展。同时讨论了B-T细胞的相互作用在BLV感染时疾病阶段性发展过程中的作用。%This review focuses on the relationship between the function of T、B lymp hocytes and the pathogenesis of Enzootic Bovine Leukosis. In BLV infection anima l, the phenotypes of B-cells lymphoma can be derived from B1a(CD5+CD11 b+), B1b(C D5-CD11b+) and conventional B2(CD5-CD11b-)cells. Co mbined with previous findi ngs the data suggests that the decrease of IL-12 and the increase of IL-10 res ult in the formation of B-cell lymphosarcoma, and the imbalance of phenotype Ⅰ and Ⅱ cytokines causes the progression of Bovine Leukemia. M eanwhile, the interaction of B and T cells could contribute to the polyclonal ac tivation and proliferation of B lymphocytes in BLV infectea animals.

  14. 中医药治疗干燥综合征及对 B 淋巴细胞的影响%Effect of Chinese medicine on Sjogren's syndrome and its B lymphocyte

    Institute of Scientific and Technical Information of China (English)

    夏莎; 纪伟

    2015-01-01

    Sjogren's syndrome (SS ) belongs to the category of “dryness syndrome” in traditional Chinese medicine ,it often occurs duo to yin deficiency and dryness-heat together with obstruction of collaterals by blood stasis ,therefore ,the methods of nourishing yin along with promoting blood circulation and removing blood stasis are often used in the treatment ,which have achieved good effect clinically .The modern medical science thinks that the etiology of SS is unknown ,but it mainly charac-terized by B lymphocytic infiltration of exocrine glands .In recent years ,the treatment of Chinese medicine on SS is more popular ,in order to make deep discussion of its mechanism of action ,more and more clinical and experimental studies have begun to discuss its effect on B cells ,and this will also become one of the hot research of traditional Chinese medicine in the treatment of SS in the futrue .%干燥综合征(Sjogren's syndrome ,SS )归属于中医“燥证”范畴,多因阴虚燥热、瘀血阻络而发病,因此治疗上常采用养阴生津、活血祛瘀的方法,临床取得了良好的疗效。现代医学认为,SS的病因不明,但主要以B淋巴细胞(简称B细胞)浸润外分泌腺为特征。近年来,中医药对SS的治疗越发普遍,为了进一步明确其作用机制,越来越多的临床研究和实验研究已开始探讨其对B细胞的影响,这将成为今后研究中医药治疗SS的热点之一。

  15. Expression of B7-related protein-1 on B lymphocytes in peripheral blood from patients with systemic lupus erythematosus and its relationship with disease activity%SLE患者外周血B细胞B7RP-1的表达及其与疾病活动度的相关性

    Institute of Scientific and Technical Information of China (English)

    陈国平; 潘海峰; 李文先; 张滔; 李静; 朱青青; 叶冬青

    2009-01-01

    Objeetive To explore the differentiation of B lymphocytes and expression of B7-related protein-1 (B7RP-1)on B lymphocytes in patients with systemic lupus erythematosus(SLE).Methods Three-color immunofluorescent staining and flow cytometric assay were used to analyze the frequency of three types of B lymphocytes,I.e.,plasma cells,memory B lyphocytes and naive B lymphocytes,as well as the expression of B7RP-1 on these cells in peripheral blood from 23 patients with SLE and 16 normal human controls.Clinical data of these patients with SLE were collected.and SLE disease activi index(SLEDAI)was also evaluated.The relationship was assessed between the expression of B7RP-1 and SLEDAI.Results The frequency of plasma cells was highest in patients with active SLE.followed by patients with inactive SLE and normal human controls(P<0.01).A significant decrease was observed in the frequency of memory B lymphocytes in patients with active SLE compared with normal controls (P<0.01),but no significant difference was found between patients with inactive SLE and those with active SLE(P>0.05).Regarding the frequency of naive B lymphocytes,there was no significant difierence among the three groups.Increased frequency of plasma cells was also noted in patients with lupus nephritis(LN)compared with those without LN [(6.15±3.12)%vs(3.31±1.41)%,P<0.05 ],but no significant difierence was found with regard to the frequency of memory or naive B lymphocytes between these two groups.The expression rate Of B7RP-1 was significantly lower on total lymphocytes from patients with SLE than from normal human controls (46.51%vs 63.75%,P<0.05),which was the case with B7RP-1 on plasma cells,memory B lyphocytes and naive B lymphocytes (all P<0.01),whereas no significant difierence was found between patients with inactive SLE and active SLE or between patients with and without LN.In addition.no correlation was found between the expression of B7RP-1 and SLEDAI(r=0.035,P>0.05).Conclusions In

  16. Guillain-Barré综合征患者B淋巴细胞辅助受体CD l9表达的研究%Expression of CO-receptor CD 1 9 on peripheral B lymphocytes in patients with Guillain-Barre syndrome

    Institute of Scientific and Technical Information of China (English)

    袁学谦; 朱太卿; 张莉峰; 王慧贞; 王焕荣; 王爱丽; 张东锋

    2011-01-01

    目的 本研究通过检测Guillain-Barre综合征(GBS)患者外周血单个核细胞CD l9蛋白的表达,探讨CD l9与GBS及其严重程度之间的关系.方法 利用流式细胞术检测GBS组(36例)和正常对照组(20例)的CD l9蛋白表达,按病程将GBS组分为急性期亚组与恢复期亚组,并分析与疾病严重程度之间的关系.结果 与正常对照组221±78个比较,GBS组742±128个B细胞数量显著升高,差异有统计学意义(P0.05).与恢复期GBS组87.27±6.04%比较,急性期GBS组81.20+5.25%CD l9+CD20+无明显差异(P>0.05).与轻症GBS组632+68个比较,重症GBS组797+130个B细胞数量无明显差异(P>0.05).与轻症GBS组82.53+5.03%比较,重症GBS组85.84+6.77%CD l9+CD20+无明显差异(P>0.05).结论 CD l9在GBS中表达显著升高,但与病程和病情严重程度无关.%Objective To explore the corlation between the expression of CD19 and the severity of GBS. The expression of CD19 of B lymphocyte in peripheral blood mononuclear cells( PBMNCs )of the disease was tested.Methods GBS group( 36 cases )and healthy controls( HC )group( 20 cases )were investigated. The expression of CD 19 on peirpheral B lymphocytes were examined by flow cytometry. According to course of disease, GBS group was divided into acute subgroup and recovery subgroup. Furthermore, the corelation between the expression of CD 19 and the severity of the disease was analyzed. Results Compared with HC group[ 221 + 78 ], B lymphocyte numbers[ 742 + 128 ]were significantly higher( P < 0. 01 ). Compared with HC group[ 62.21 + 7. 85% ], the CD 19 + CD20+ increased significantly ( P <0.0 1 )in GBS group[ 83.92 +6.23% ]. Compared with recovery subgroup[ 686 + 108 ],B lymphocyte numbers were of no significant differences( P > 0.05 )in the acute subgroup[ 810 + 124 ]. Compared with recovery subgroup[ 87.27 + 6.04% ], the CD19 + CD20 + was of no significant differences( P > 0.05 ) in the acute subgroup[ 81.20 + 5.251% ]. Compared with mild

  17. Roles of B lymphocyte and plasma cell in liver allograft of acute and chronic rejection%肝脏移植急、慢性排斥反应时移植肝内B淋巴细胞和浆细胞的变化和意义

    Institute of Scientific and Technical Information of China (English)

    宋继勇; 石炳毅; 杜国盛; 朱志东; 邹一平; 金海龙

    2010-01-01

    Objective To explore the roles of B lymphocyte and plasma cell in liver allograft re-jection to find the evidences of humoral factor participating in the rejection. Methods Immunohisto-chemical inspection of C4d, CD20+ B lymphocytes and CD138+ plasma cells were performed in 34 liver biopsy specimens from 25 patients with hepatic injury and their preoperative specimens. Then we ob-served the variances of the above parameters in the liver biopsy specimens and the differences of them with different hepatic injuries. We further observed the relation of the presence of CD20+ B lympho-cytes and CD138+ plasma cells to C4d positivity. Meanwhile, we compared the difficulties of clinical therapy with different presences of CD20+ B lymphocytes and CD138+ plasma cells in the liver biopsy specimens. Results The positive ratios of CD20+B lymphocytes and CD138+ plasma cells were signif-icantly higher in the acute rejection group than in the non-rejection group(P<0. 05 and P<0. 01).The positive ratios of CD20+ B lymphocytes were markedly higher in the chronic rejection group than in the non-rejection group(P<0. 05). There was no difference in CD138+ plasma cells between the 2 groups. The degrees of hepatic injury could not influence the positive ratioes of CD138+ plasma, but the positive ratioes of CD20+ B lymphocytes in the heavy hepatic injury groups was higher than in the slight hepatic injury groups(P<0. 05). CD20+ B lymphocytes and CD138+ plasma cells presented fol-lowing C4d(P<0. 01 and P<0. 05). The effective power of steroid in the all-positive group was obvi-ously lower than in the all-negative group(P<0. 05). Conclusion Humoral immune may participate in some liver allograft rejection. It would be more favorable for observing and prewarning the humoral re-jection by finding CD20, CD138 and C4d by immunohistochemical staining in liver biopsy specimens with hepatic injury after liver transplantation. It would be helpful for choosing the therapeutic regi-mens of liver

  18. 单纯疱疹病毒Ⅰ型的Th细胞和B细胞表位重组核酸疫苗的构建及真核表达%Construction and Eukaryotic Expression of HSV?1 Th and B Lymphocytes Recombinant Multi?epitope DNA Vaccine

    Institute of Scientific and Technical Information of China (English)

    刘贤洁; 孙原; 马小力

    2015-01-01

    Objective To construct the recombinant multi?epitope DNA vaccine of HSV?1 Th and B lymphocytes of gB?gD protein,and to identify its eukaryotic expression. Methods The epitopes of HSV?1 gB?gD protein were analyzed by bioinformatics analysis software. HSV?1 Th and B lym?phocyte recombinant multi?epitope gene(Th/B gene)was designed and synthesized. Th/B gene was cloned into pVAX1 to synthesize pVAX1?Th/B. pVAX1?Th/B was then transfected into COS?7 cell,and the protein expression was identified by Western blot. Results The epitopes of Th and B lymphocytes of HSV?1 gB and gD were predicted,and the eukaryotic expression plasmid pf pVAX1?Th/B was successfully constructed and con?firmed by sequencing. In addition,the in vivo protein expression of the recombinant DNA was confirmed by Western blot. Conclusion HSV?1 Th and B lymphocyte recombinant multi?epitope DNA vaccine was successfully synthesized in this study. HSV?1 Th and B lymphocyte recombinant multi?epitope DNA vaccine can be successfully expressed in isolated eukaryotic cells. This study provides a feasible solution for developing DNA vac?cine against HSV?1 infection.%目的 构建单纯疱疹病毒Ⅰ型(HSV?1)糖蛋白B(gB)和糖蛋白D(gD)的Th细胞和B细胞表位重组串联核酸疫苗,并鉴定其真核表达.方法 利用生物信息学分析软件预测HSV?1 gB和gD的Th细胞表位和B细胞表位,结合已发表文献,设计合成HSV?1的Th细胞和B细胞表位重组串联抗原基因(Th/B基因).将Th/B基因定向克隆入真核表达载体pVAX1,构建真核表达质粒pVAX1?Th/B.用制备的质粒转染COS?7细胞,裂解细胞后经Western blot鉴定其蛋白表达.结果 预测得到了HSV?1 gB和gD的Th细胞和B细胞表位,成功构建真核表达质粒pVAX1?Th/B,经测序确认序列正确.SDS?PAGE分离出相应大小的蛋白表达片段,经Western blot鉴定并证实该重组核酸疫苗能够在体外真核细胞中表达.结论 成功构建HSV?1 Th细胞和B细胞表位重组串联核酸

  19. Study of the relationship between Epstein-Barr virus infection and abnormal activation of B-lymphocytes in systemic lupus erythematosus%EB病毒感染与系统性红斑狼疮患者外周血中B淋巴细胞异常活化的相关性研究

    Institute of Scientific and Technical Information of China (English)

    李毅

    2009-01-01

    Objective To investigate the role of Epstein-Barr virus(EBV) infection on the abnormal activation of peripheral B-iymphocytes of systemic lupus erythematosus (SLE) patients,and the relationship between EBV infection and the abnormal activation of B-lymphocytes and SLE activity is explored. Methods BamH I-W genome in EBV DNA of 52 SLE patients and 23 controls were examined by PCR-Southern blotting. The level of ANA and EBV VCA-IgM in sera was measured by ELISA. The expression of CD19+ and expression rate of CD19+ and CD23+/CD19+ in EBV-positive SLE patients was higher than that of EBV-negative patients. Meanwhile,the fluorescence signal of CD23 in B cell of EBV-positive SLE patients was stronger than that of EBV-negative ones. Conclusion EBV infection may be related to abnormal activation of B-lymphocytes.EBV may infect and activate B-lymphocytes by up regulating the expression of CD23 of B-lymphocytes. The abnormal activation of B-lymphoeytes is associated with SLE activity.%目的 研究EB病毒(EBV)感染与系统性红斑狼疮(SLE)患者外周血B淋巴细胞异常活化及疾病活动性的关系,探讨EBV在SLE病因学研究中的意义.方法 应用聚合酶链反应(PCR)-Southern杂交技术检测52例SLE患者和23名健康对照组外周血中EBV特异性BamH I-W基因片段;同时应用流式细胞术检测患者及对照组外周血中CD19+、CD23+/CD19+B淋巴细胞的表达情况.结果 ①PCR-Southern杂交检测结果显示SLE患者组EBV特异性BamH I-W片段阳性率明显高于健康对照组(P<0.01).②活动期SLE患者组CD23+/CD19+双阳性细胞的表达率与稳定期及健康对照组比较差异均有统计学意义(P<0.01).③EBV-DNA阳性患者组CD19+及CD23+/CD19+细胞的表达率明显高于EBV-DNA阴性SLE组(P<0.05);EBV-DNA阳性患者组CD19+B淋巴细胞表达CD23的平均荧光强度明显高于E-BV-DNA阴性患者组(P<0.01).结论 SLE患者体内EBV感染与B淋巴细胞异常活化有一定的相关关系,EBV可能通过

  20. Plasma from patients with systemic lupus erythematosus inhibits suppressive activity of mesenchymal stem cells against lupus B lymphocytes%系统性红斑狼疮患者血浆降低间充质干细胞对B淋巴细胞的抑制作用

    Institute of Scientific and Technical Information of China (English)

    聂瑛洁; 罗利梅; 查艳; 孙立; 骆辑; 潘润桑; 田晓滨

    2016-01-01

    Objective To investigate whether plasma from patients with systemic lupus erythematosus (SLE) inhibits the suppressive effects of mesenchymal stem cells (MSCs) on lupus B lymphocytes. Methods MSCs isolated and expanded from the bone marrow of healthy donors were co-cultured with B cells purified from the peripheral blood of SLE patients in the presence of fetal bovine serum or pooled plasma from SLE patients, and the proliferation and maturation of the B lymphocytes were analyzed. Results Co-culture with normal MSCs obviously inhibited the proliferation of lupus B cells and suppressed the maturation of B lymphocytes, which showed lowered expressions of CD27 and CD38. The pooled plasma from SLE patients significantly inhibited the suppressive effects of normal MSCs on B cell proliferation and maturation. Conclusion Plasma from SLE patients negatively modulates the effects of normal MSCs in suppressing lupus B cell proliferation and maturation to affect the therapeutic effect of MSC transplantation for treatment of SLE. Double filtration plasmapheresis may therefore prove beneficial to enhance the therapeutic effects of MSC transplantation for SLE.%目的:研究系统性红斑狼疮(SLE)患者血浆对健康人骨髓来源的间充质干细胞(MSCs)免疫抑制作用的影响。方法采用SLE患者富集血浆替代胎牛血清,共培养MSCs与SLE患者的B淋巴细胞,检测MSCs对B淋巴细胞增殖能力与成熟的影响。设置胎牛血清作为对照组。数据采用SPSS12.0软件进行学生t检验统计学分析,P<0.05认为差异有统计学意义。结果正常MSCs能抑制脂多糖刺激的SLE患者来源B细胞增殖,降低B细胞表面表达的CD27与CD38。SLE患者富集血浆能抵制MSC对B淋巴细胞增殖与成熟的抑制作用。结论正常MSCs能抑制SLE患者B淋巴细胞增殖与成熟,改变B淋巴细胞亚群所占比例。SLE患者血清能抑制MSCs对B淋巴细胞的免疫抑制作用,或将负向影响间充

  1. 乳源β Casein 125肽的基本特征及促B淋巴细胞增殖作用%Basic characteristics of a human milk-derived peptide β-Casein-125 and its effect on B lymphocyte proliferation

    Institute of Scientific and Technical Information of China (English)

    刘贵友; 万俊; 肖文

    2016-01-01

    The biologic characteristics of β⁃Casein⁃125 peptide were analyzed by Uniprot, SABLE, ProtParam tool and other online databases. The content ofβ⁃Casein⁃125 in colostrum, transition milk and mature milk was mesured by mass spectrometry technology. Furthermore, the effect of β⁃Casein⁃125 peptide in B lymphocyte proliferation was evaluated by MTT assay. The online databases showed that stability coefficient, aliphatic index and grand average of hydropathicity of β⁃Casein⁃125 were 111�43, 111�43 and 0�471, respectively. It indicated that β⁃Casein⁃125 is a hydrophobic stable peptide. The content of β⁃Casein⁃125 was significantly decreased with lactation time, detected by mass spectrometry technology. Moreover, β⁃Casein⁃125 could across the cell membrane of mouse B lymphocytes, and promote their proliferation. β⁃Casein⁃125, a hydrophobic peptide with high stability, could promote lymphocyte proliferation. It was indicated thatβ⁃Casein⁃125 played a critial role in promoting the neonatal immune system maturation.%利用Uniprot、SABLE、ProtParam tool等在线数据库分析β Casein 125肽生物学特征;利用质谱定量技术检测β Casein 125肽在初乳、过渡乳和成熟乳中的含量变化;利用细胞增殖实验方法揭示β Casein 125肽在促进B淋巴细胞增殖中的作用。结果表明:β Casein 125肽的稳定性系数为111�43,脂肪指数和亲水性分别为111�43和0�471,属于疏水性稳定型多肽。质谱定量分析发现:β Casein 125肽含量随泌乳时间变化含量显著降低。β Casein 125肽不仅可以顺利进入小鼠B淋巴细胞,并且可显著促进细胞增殖。β Casein 125肽具有高稳定性和疏水性的特征,可以促进淋巴细胞增殖,提示该肽可能在新生儿免疫系统建立中发挥重要作用。

  2. 系统性红斑狼疮患者外周血B细胞脂筏及细胞骨架蛋白的表达初探%Study on the expression of lipid rafts and F-actin in peripheral blood B lymphocytes from patients with systemic lupus erythematosus

    Institute of Scientific and Technical Information of China (English)

    何德宁; 董光富; 张晓; 张光锋; 谢悦胜; 李玲; 雷云霞

    2012-01-01

    Objective To investigate the expression of lipid rafts (LRs) and actin cytoskeleton (F-actin) in the peripheral blood B lymphocytes of patients with systemic lupus erythematosus (SLE).Methods Peripheral blood mononuclear cells (PBMCs) were separated by Ficoll-Hypaque.B lymphocytes were isolated by positive selection from PBMCs.Membrane staining for LRs was achieved with FITC-conjugated cholera toxin B (CTB).The level and distribution of LRs were studied by flow cytometry and confocal microscopy.Staining for F-actin was carried out with Rhodamine phalloidin.The expression of F-actin was analyzed by confocal microscopy.In an in vitro examination,the effect of Leflunomide on lipid rafts in B lymphocytes from SLE was analyzed.Disease carried out was measured using the SLE disease activity index (SLEDAI).Analysis of the enumerical data was performed using ANOVA or paired-samples t test.Correlation was examined by Pearson's rank correlation test.Results The number of CTB-binding lipid rafts in B cell from active SLE patients or from SLE patients in disease remission.who were treated with immunosuppressive drugs was higher than B cells from healthy controls [(59+4)%,(51±5)%,(33±4)%,F=9.21,P=0.001].Confocal microscopy revealed that in B cell from healthy controls,lipid raft was found to be small and uniformly distributed on the plasma membrane.F-actin was found mainly in the cortical region of the cells.This pattern was different from the pattern seen in B cells from patients with SLE,which presented with stronger staining and irregular large clustering of LRs,with a decrease in F-actin levels.In addition,the number of CTB-binding LRs in B cells from the active SLE patients was correlated significantly with the SLEDAI score (r=0.632,P=0.028).Furthermore,thein vitro results showed that leflunomide treatment reduced the number of CTB-binding LRs in B cell from SLE patients [(48±5)% vs (39±5)%,t=2.29,P=0.048].Conclusion The altered expression of Lipid raft and F

  3. 肾组织B淋巴细胞浸润及其异位淋巴样组织形成在狼疮肾炎诊治中的意义%Patterns of B Lymphocytes Infiltration in Kidney from Patients with Lupus Nephritis

    Institute of Scientific and Technical Information of China (English)

    龙康霞; 董光富; 张晓; 张光峰

    2016-01-01

    Objective To understand the value of B lymphocytes infiltration and associated ectopic lymphoid tissue ( ELT) formation in the diagnosis and treatment of lupus nephritis ( LN) .Methods Eight-nine cases of established LN patients were enrolled.The renal specimen were analyzed by light microscopy examination for routine pathology and immunohistochemistry was used to the detection of expression of CD3 +T lymphocytes, CD20 +B lymphocytes and CD21 +Follicular dendritic cells ( FDCs) .All patients had received traditional high-dose glucocorticoid ( GC ) and immunosuppressants ( IS ) . Results Pathology analysis showed B and T lymphocyts infiltration mainly located at the interstitial region with 77 cases ( 86.5%) , at peritubular area in 9 cases and periglomerular area in 3 cases.WHO Ⅲ 21 (23.6%), WHO Ⅳ53 (59.6%) and WHOⅤ15 (16.8%) LN were diagnosed.Based on whether or not there was CD20 +cells expression in renal tissues , 69 cases were CD20 +cells ( 77.5%) and 20 were CD20-cells (22.5%) .Compared to the CD20-group, significant difference could be found in the CD20 +group at a mean disease duration ( CD20 +group: 21.8 ±9.9 months vs.CD20-group:9.8 ±6.2 months, P =0.045 ) and complete disease remission rate ( CD20 +group: 63.8% vs. CD20-group:90%, P=0.047 ) after 6 months of treatment.For B lymphocytes infiltration associated ELT formation, focal distribution of CD3 +T cells and CD20 +B cells (type 2) could be observed in 51 cases (57.3%) , scattering distribution of CD3 +T cells and CD20 +B cells ( type 1) were found in 18 cases (20.2%) and no CD20 +B cells infiltration in 20 cases (22.5%) but no expression of CD21 +FDCs expression in all.The disease duration was longer in type 2 ELT patients than those in type 1 or type 0 ELT patients.Compared to WHO Ⅴ-LN patients, there were different ELT distribution patterns in WHOⅢand WHOⅣ-LN patients, but there were no difference in ELT distribution patterns between WHO Ⅲ and WHO Ⅳ-LN patients. Conclusion

  4. Epigenetic Regulation of B Lymphocyte Differentiation, Transdifferentiation, and Reprogramming

    Directory of Open Access Journals (Sweden)

    Bruna Barneda-Zahonero

    2012-01-01

    Full Text Available B cell development is a multistep process that is tightly regulated at the transcriptional level. In recent years, investigators have shed light on the transcription factor networks involved in all the differentiation steps comprising B lymphopoiesis. The interplay between transcription factors and the epigenetic machinery involved in establishing the correct genomic landscape characteristic of each cellular state is beginning to be dissected. The participation of “epigenetic regulator-transcription factor” complexes is also crucial for directing cells during reprogramming into pluripotency or lineage conversion. In this context, greater knowledge of epigenetic regulation during B cell development, transdifferentiation, and reprogramming will enable us to understand better how epigenetics can control cell lineage commitment and identity. Herein, we review the current knowledge about the epigenetic events that contribute to B cell development and reprogramming.

  5. Role of Histone Deacetylase HDAC7 in B Lymphocyte Biology

    OpenAIRE

    Román González, Lidia

    2014-01-01

    El desarrollo de células B es el resultado de varios procesos de especificación, compromiso y diferenciación, cada uno de los cuales se caracterizan por la activación de un nuevo programa de transcripción génica y la extinción del anterior. Hasta la fecha, la regulación positiva durante el desarrollo de células B llevada a cabo por factores de transcripción específicos está bien establecida. Sin embargo, los mecanismos por los cuales los factores de transcripción median procesos de represión ...

  6. Study on the expression of T, B lymphocyte antigen and platelet antibodies in patients with platelet transfusion refractoriness%血小板输注无效患者T、B淋巴细胞抗原和血小板抗体表达的研究

    Institute of Scientific and Technical Information of China (English)

    杜春红; 黄海涛; 苑广洋; 赵国生; 李红学; 张元; 孙亚军; 徐慧民; 董守智

    2016-01-01

    Objective To explore whether T lymphocytes subgroup,B lymphocytes,platelet antigen CD41a,CD61 or platelet antibodies are involved in the platelet transfusion refractoriness.Methods Forty-seven patients diagnosed as platelet transfusion refractoriness and 32 patients that achieved effective platelet therapy were ennolled in this study.Flow cytometry was performed to detect the proportion of cytotoxic T cell (CD3+CD4-CD8+),helper T cell (CD3+CD4+CD8) and B lymphocytes (CD19+),and the expression of platelet glycoproteins,including CD41a and CD61,while platelet antibodies were also measured by solid-phase agglutination.Results The significant lower level of helper T cell (36.60% vs 48.53%),higher level of cytotoxic T cell (53.26% vs 44.02%) and lower cytotoxic/helper T cell ratio (0.85 vs 1.31) were observed in platelet refractoriness group when compared with effective platelet therapy group (P<0.05).However,the significant difference was not observed in B lymphocytes between the two group (3.02% vs 2.85%,P>0.05).Platelet glycoproteins CD41 a and CD61 and antibodies were both expressed at high levels in platelet refractoriness group (88.10% vs 51.69%,88.36% vs 51.83%,85.37% vs 14.82%,respectively,P<0.05).Conclusions Activation of cytotoxic T cells,suppression of helper T cells,higher expression level of platelet glycoproteins CD41a and CD61 as well as the development of anti-platelet antibodies are involved in the immunologic mechanism of platelet refractoriness.%目的 探讨T、B淋巴细胞,血小板膜糖蛋白和血小板抗体在血小板输注无效中作用.方法 选择41例临床确诊血小板输注无效患者为研究对象,以27例血小板输注有效患者为对照组,采用流式细胞术检测两组患者外周血细胞毒性T淋巴细胞(CD3+CD4-CD8+)、辅助性T淋巴细胞(CD3+CD4+CD8)、B淋巴细胞(CD19+)比例和血小板膜糖蛋白CD41a、CD61的表达,采用固相凝集法检测两组患者血

  7. B淋巴细胞诱导成熟蛋白-1对多发性骨髓瘤中浆细胞分化和存活调控作用的研究进展%Research progress of B lymphocyte induced maturation protein-1 on regulation of differentiation and survival of plasma cells in multiple myeloma

    Institute of Scientific and Technical Information of China (English)

    张倩男; 姚瑶; 李振宇

    2016-01-01

    多发性骨髓瘤(MM)是一类浆细胞恶性克隆性疾病.近年其发病率呈逐年上升趋势,且迄今尚无治愈方法.从浆细胞分化和存活的调控机制入手,探索MM治疗的新靶点和新策略是一可行的治疗手段.B淋巴细胞诱导成熟蛋白(Blimp)-1是调控浆细胞分化和存活的关键转录因子,但对其在MM中作用的研究迄今尚少.相关研究结果显示,骨髓瘤细胞高表达Blimp-1,RNA干扰沉默Blimp-1表达,可使浆细胞分化消失并伴各型免疫球蛋白(Ig)合成障碍,从而抑制骨髓瘤细胞增殖并诱导其凋亡.笔者拟就Blimp-1调控浆细胞分化和存活在MM中的作用的研究进展进行综述.%Multiple myeloma (MM) is an incurable plasma malignancy and currently the incidence goes up annually.There is one of feasible methods to explore new targets and strategies for the treatment of MM from the regulation of differentiation and survival of plasma cells.B lymphocyte induced maturation protein(Blimp)-1 is a key transcription factor to regulate differentiation and survival of plasma cells,but up to now,items of research articles on Blimp--1 mechanism in MM are very liffle.Related research has shown that myeloma cells highly expressed Blimp-1 and RNA interference silencing Blimp-1 expression eradicated plasma cell differentiation and made each kind of immunoglobulin (Ig) synthesis disorder,thus inhibiting myeloma cells proliferation and inducing its apoptosis.This review focused on the research progress of Blimp-1 on regulation of differentiation and survival of plasma cells in MM.

  8. 重组人B淋巴细胞刺激因子受体-抗体融合蛋白(RCT-18)对大鼠的致畸作用%Teratogenicity and developmental toxicity of recombinant B lymphocyte stimulating factor receptorantibody fusion protein (RCT-18) in rats

    Institute of Scientific and Technical Information of China (English)

    张立将; 宣尧仙; 由振强; 宋翼升; 陈颖; 陈浩; 张丽丽; 黄敏; 王文祥; 房健民

    2012-01-01

    OBJECTIVE: To evaluate the teratogenicity and developmental toxicity of recombinant B lymphocyte stimulating factor antagonist-antibody fusion protein (RCT-18) in Sprague-Dawley (SD) rats. METHODS: Mated female rats were randomly segregated into four groups, including three RCT-18 groups (11, 37 and 129 mg/kg) and one negative control group (sodium chloride injection), with more than 25 rats in each group. RCT-18 was administered via subcutaneous injection to timed pregnant rats on gestation days (GD) 6-15 every two days. Clinical signs, body weights, and feed consumption were monitored during the whole gestation. Caesarean section and autopsy were performed on GD20. Uterine content were evaluated for number of implantations, resorptions, live and dead fetuses. The number of corpora lutea in each ovary was also recorded. Live fetuses were examined for gender, body weights, body lengths, tail lengths, and gross external, visceral and skeletal changes. RESULTS: There were no significant differences in maternal and embryo-fetal parameters. CONCLUSION: No maternal toxicity and embryo-fetal toxicities were found when RCT-18 was administered to SD rats during GD 6-15.%目的:观察重组人B淋巴细胞刺激因子受体-抗体融合蛋白(RCT-18)对大鼠胚胎及胎仔的发育毒性和致畸作用.方法:采用雌性SD大鼠,交配成功后随机分为4组,即RCT-18高(129 mg/kg)、中(37 mg/kg)、低(11 mg/kg)剂量组及阴性对照(0.9%NaCl注射液)组,每组≥25只,于妊娠第6~15天连续5次(隔天1次)经皮下注射给药.实验过程中观察动物的一般反应、体质量、摄食量变化,于妊娠第20天解剖孕鼠,对着床、吸收胎、死胎、活胎、黄体进行计数,对胎仔的体质量、身长、尾长,以及外观形态、内脏和骨骼发育等指标进行评价.结果:孕鼠、胚胎形成、胎仔生长发育、外观形态、内脏和骨骼发育等各项指标均无明显异常,与阴性对照组

  9. Expression of the fusion protein of human soluble B lymphocyte stimulator and diphtheria toxin in E. coli and its biological activity%人sBAFF-DT388融合蛋白在大肠杆菌中的表达及其活性研究

    Institute of Scientific and Technical Information of China (English)

    朱月婷; 焦玉莲; 崔彬; 张捷; 游力; 赵跃然

    2011-01-01

    Objective To prepare the fusion protein of human soluble B lymphocyte stimulator and diphtheria toxin (hsBAFF-DT388) in E. coli and investigate its targeted activity to human B cells. Methods The hsBAFF-DT388 gene was optimized in advance and inserted into the clone vector pMD19-T. The fragment of the hsBAFF-DT388 fusion gene was separated from the plasmid pUC57-hsBAFF-DT388 by PCR according to hsBAFF-DT388 gene order. The recombinant was screened with colony PCR, restriction map analysis and DNA sequencing. The recombinant vector was digested by restriction enzymes, and then inserted into the expression vector pCold Ⅱ. The positive recombinant expression vector was identified by colony PCR and restriction map analysis. The recombinant strain was induced by IPTG. The recombinant protein was identified by SDS-PAGE and Western blot, and then purified by Ni2 + -NTA affmity chromatography. Biological activity of the purified protein was detected by cell fluoresce and MTT assay. Results Expression level of the recombinant protein accounted for 40% of total bacterial proteins of E. coli, and the recombinant protein could bind with BAFF receptor-positive cells and had a cytotoxic effect on human B cells ( Hmy2. CIR). Conclusion The fusion protein expression vector of hsBAFF-DT388 was successfully constructed and the recombinant protein with selective cytotoxicity against B cell was obtained, which may establish a solid foundation for further study of the therapy for B cell malignancies and autoimmune diseases.%目的 制备人B淋巴细胞刺激因子-白喉毒素融合蛋白(hsBAFF-DT388),探讨其靶向B细胞活性.方法 根据优化合成的hsBAFF-DT388基因序列设计引物,PCR扩增目的 基因并插入克隆载体pMDl9-T,采用菌落PCR、酶谱分析及DNA测序鉴定阳性克隆,重组克隆载体经双酶切后插入表达载体pColdⅡ,并鉴定重组表达载体.重组菌株经ITPG诱导,SDS-PAGE分析及Western blot鉴定,经Ni2+-NTA层析柱纯化,

  10. CD86嵌合抗体对系统性红斑狼疮患者自身反应性B细胞的作用及影响研究%Effects of an anti-CD86 chimeric antibody (ch1D1) on autoreactive B lymphocytes isolated from pa-tients with SLE

    Institute of Scientific and Technical Information of China (English)

    刘玉华; 陈兆军; 韩杰; 潘峰; 鄢巨振; 张腊红; 郑小银; 刘杨

    2016-01-01

    目的:探讨CD86嵌合抗体ch1D1对系统性红斑狼疮( systemic lupus erythematosus, SLE)患者自身反应性B细胞的作用及影响。方法利用流式细胞术分析SLE患者B细胞表面CD86的表达水平及ch1D1对SLE患者CD4+T细胞活化的影响;利用磁珠法分选出健康志愿者和SLE患者外周血单个核细胞( PBMC)中的B细胞、NK细胞以及CD4+T细胞用于后续实验;利用LDH释放法检测ch1D1介导对SLE患者B细胞的抗体依赖的细胞介导的细胞毒作用( antibody dependent cell medi-ated cytotoxicity,ADCC)及补体依赖的细胞介导的细胞毒作用( complement dependent cell mediated cy-totoxicity,CDC),利用ELISA法检测ch1D1对SLE患者B细胞分泌自身抗体的影响,利用3H掺入法分析ch1D1对SLE患者CD4+T细胞增殖的影响。结果 SLE患者B细胞上CD80(68.08±14.28 vs 46.10±12.14,n=24,P<0.0001)和CD86(44.72±14.90 vs 13.99±10.74,n=24,P<0.0001)的表达水平显著高于健康志愿者,提示B细胞异常活化;与对照组相比,ch1D1能更有效介导对SLE患者B细胞的ADCC和CDC作用(P=0.0172,P=0.0388);活化的T细胞显著增强SLE患者B细胞产生自身抗体,ch1D1显著抑制了SLE患者自身抗体的分泌(P=0.0019);SLE患者CD4+T细胞活化和增殖水平显著高于健康志愿者,而ch1D1显著抑制 SLE患者 CD4+T细胞的增殖和活化( P=0.0024,P=0.0495)。结论 CD86嵌合抗体能更有效地介导对SLE患者自身反应性B细胞的ADCC和CDC作用,抑制其自身抗体的分泌,抑制自身反应性CD4+T细胞的增殖和活化,有望成为治疗SLE的新型免疫制剂。%Objective To investigate the effects of ch1D1, an anti-CD86 chimeric antibody, on autoreactive B lymphocytes isolated from patients with systemic lupus erythematosus ( SLE) . Methods Flow cytometry analysis was performed to measure the expression of CD86 on the surface of B cells isolated from patients with SLE and to analyze the effects of ch1D1 on the activation of CD4+T cells

  11. Study of biologic characteristics on Epstein-Barr virus transformed B lymphocytes carrying hepatitis C virus type Ⅱ%丙型肝炎病毒Ⅱ型阳性PBMC永生化细胞株的生物学特性

    Institute of Scientific and Technical Information of China (English)

    程计林; 仝文斌; 冯百芳; 陶其敏; 朱伟; 刘宝玲; 陈良标; 陈佩兰

    2001-01-01

    Objective To study persistence and replication of hepatitis C virus (HCV) in the patients′ peripheral blood mononuclear cells (PBMC) transformed by Epstein-Barr virus (EBV) in vitro and in order to explore the possibility of establishing a cell line for HCV reproduction. Methods EBV infected peripheral B lymphocytes from one patient with HCV positive of PBMC were transformed into permanent lymphoblastoid cell lines (LCL). The general and special biology characteristics of LCL were studied by cell culture, chromosome banding technique, flow fluorescent-activated cell sorter, reverse transcription-polymerase chain reaction (RT-PCR), in situ PCR, immunohistochemistry and electronic microscopy. Results 1. G-banded karyotype of the LCL was 47, XX, +mar, CD19 and CD20, CD antigens of LCL cell surface were positive and CD21 was not expressed. 2. Positive and negative HCV RNA strands from cultured cells and supernatants were detected by RT-PCR every month. HCV RNA plus strands persisted in the cultured cells for more than one year. It is interesting that the minus-strand RNA in LCL and the plus-strand RNA in supernatants were observed intermittently and HCV genome type of the LCL was type Ⅱ. 3. Immunohistochemical study found that HCV NS3 and C proteins were mostly expressed in LCL cytoplasm. In situ PCR showed that HCV RNA positive signal was mainly located in LCL cytoplasm. Electronic microscopy found HCV spherical virus-like particles with diameter of approximately 45 to 70nm, some particles were 110nm in LCL cytoplasmic vesicles. Conclusion HCV may exist in LCL cultured cells for a longer period and reproduce in and secrete into the media. It offers a strong evidence for persistence of HCV RNA in PBMC of HCV-infected patients.%目的观察丙型肝炎病人外周血B细胞长期存活状态下其中是否仍有丙型肝炎病毒(HCV)存在,探讨建立HCV体外复制细胞模型的可能性。方法利用EB病毒转化B淋巴细胞技

  12. B淋巴细胞刺激因子对慢性特发性荨麻疹患者产生抗FcεRI抗体和抗IgE抗体的影响%The Affect of the Serum B Lymphocytes Stimulating Factor(BlyS)on the Anti-IgE Antibody and Anti-FcεRI Antibody of the Patients with Chronic Idiopathic Urticaria

    Institute of Scientific and Technical Information of China (English)

    李正学

    2015-01-01

    目的:探讨慢性特发性荨麻疹患者血清B淋巴细胞刺激因子(BlyS)对抗IgE抗体和抗FcεRI抗体的影响。方法:选取慢性特发性荨麻疹患者100例作为疾病组,选取同期体检健康者100例作为健康组。检测两组受试者血清BlyS、抗IgE抗体及抗FcεRI抗体水平;分离培养疾病组患者外周血中的B淋巴细胞,分为两份保存,在其中一份培养液中加入有效水平的BlyS,检测抗IgE抗体及抗FcεRI抗体水平,作为试验组,将另一份作为空白对照组。分析血清BlyS与抗IgE抗体及抗FcεRI抗体之间的关系。结果:疾病组血清BlyS、抗IgE抗体及抗FcεRI抗体水平明显高于健康组,差异具有统计学意义(P<0.05)。试验组培养液中抗IgE抗体及抗FcεRI抗体水平明显高于对照组,差异具有统计学意义(P<0.05);试验组中抗IgE抗体及抗FcεRI抗体水平与BlyS呈正相关(r=0.765、0.722,P<0.05)。结论:慢性特发性荨麻疹患者血清BlyS可刺激B淋巴细胞产生抗IgE抗体和抗FcεRI抗体,这可能与慢性特发性荨麻疹的发病机制有关。%Objective:To investigate the affect of the serum B lymphocytes stimulating factor(BlyS)on the anti-IgE antibody and anti-FcεRI antibody of the patients with chronic idiopathic urticaria. Method:100 cases of patients with chronic idiopathic urticaria were selected as disease group,100 cases of healthy people in the same period were selected as the healthy group. The serum level of the BlyS,anti-IgE antibody and anti-FcεRI antibodies were detected;the B lymphocytes from the peripheral blood of the disease group patients were isolated and cultured,and divided into two shares,add BlyS in one share as the experimental group,another share as blank control group,the level of the anti-IgE antibody and anti-FcεRI antibodies were detected. The relationship among the BlyS,anti-IgE antibody and anti-FcεRI antibodies were analyzed. Result

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

    Science.gov (United States)

    1982-05-01

    Bethesda. MO). Proprtis an exresion f mmbrae atigns (, 2 In The goat anti-p antiserum from which the specifically purified antibodies and xpresio of embane...cell * Independent responses in B-cell defective CsA/N mice to Brucella abortus cycle by ProPiumn iodide staining. J. Cell. Bil. 66:188. and to TNP

  14. Microenvironments of T and B lymphocytes : a light- and electromicroscopic study

    NARCIS (Netherlands)

    W. van Ewijk (Willem)

    1977-01-01

    textabstractPeripheral blood cells- erythrocytes, granulocytes, monocytes, thrombocytes and lymphocytes-are the end products of a differentiation process which occurs in the bone marrow and, in rodents, also in the spleen. Normal haemopoietic tissue is a cell renewal system with an accurate balance

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

    Science.gov (United States)

    2015-10-01

    the kinase NIK. Nat Immunol 2008, 9:1371–1378. 71. Vince JE, Wong WW, Gentle I, Lawlor KE, Allam R, O’Reilly L, Mason K, Gross O, Ma S, Guarda G, et...development. Immunity 2003, 19:353–363. 278. Yang YJ, Chen W, Carrigan SO, Chen WM, Roth K, Akiyama T, Inoue J, Marshall JS, Berman JN, Lin TJ: TRAF6...potential. Chem Biol 2013, 20:316–331. 66. Szklarczyk D, Franceschini A, Kuhn M, Simonovic M, Roth A, Minguez P, Doerks T, Stark M, Muller J, Bork P

  16. Gammaherpesvirus-driven plasma cell differentiation regulates virus reactivation from latently infected B lymphocytes.

    Science.gov (United States)

    Liang, Xiaozhen; Collins, Christopher M; Mendel, Justin B; Iwakoshi, Neal N; Speck, Samuel H

    2009-11-01

    Gammaherpesviruses chronically infect their host and are tightly associated with the development of lymphoproliferative diseases and lymphomas, as well as several other types of cancer. Mechanisms involved in maintaining chronic gammaherpesvirus infections are poorly understood and, in particular, little is known about the mechanisms involved in controlling gammaherpesvirus reactivation from latently infected B cells in vivo. Recent evidence has linked plasma cell differentiation with reactivation of the human gammaherpesviruses EBV and KSHV through induction of the immediate-early viral transcriptional activators by the plasma cell-specific transcription factor XBP-1s. We now extend those findings to document a role for a gammaherpesvirus gene product in regulating plasma cell differentiation and thus virus reactivation. We have previously shown that the murine gammaherpesvirus 68 (MHV68) gene product M2 is dispensable for virus replication in permissive cells, but plays a critical role in virus reactivation from latently infected B cells. Here we show that in mice infected with wild type MHV68, virus infected plasma cells (ca. 8% of virus infected splenocytes at the peak of viral latency) account for the majority of reactivation observed upon explant of splenocytes. In contrast, there is an absence of virus infected plasma cells at the peak of latency in mice infected with a M2 null MHV68. Furthermore, we show that the M2 protein can drive plasma cell differentiation in a B lymphoma cell line in the absence of any other MHV68 gene products. Thus, the role of M2 in MHV68 reactivation can be attributed to its ability to manipulate plasma cell differentiation, providing a novel viral strategy to regulate gammaherpesvirus reactivation from latently infected B cells. We postulate that M2 represents a new class of herpesvirus gene products (reactivation conditioners) that do not directly participate in virus replication, but rather facilitate virus reactivation by manipulating the cellular milieu to provide a reactivation competent environment.

  17. Expression of IL-4 receptor on human T and B lymphocytes.

    Science.gov (United States)

    Zola, H; Flego, L; Weedon, H

    1993-08-01

    The expression of the interleukin-4 receptor on human blood and tonsil lymphocytes has been studied using a monoclonal antibody and high-sensitivity immunofluorescence flow cytometry. While no receptor expression could be detected on circulating or tonsil T cells, a subset of B cells was shown to express the receptor. The IL-4R-positive B cells in tonsil had a phenotype suggesting that they included both germinal centre B cells and B cells outside the germinal centre. The subset of B cells in the blood that expressed the receptor included CD23-positive B cells. Activation of tonsil B cells using anti-IgM, IL-4, IL-2, or combinations of these reagents led to increases in IL-4R expression, but these changes were small compared to changes in the expression of IL-2R p55 (CD25), a known marker of activation. Similarly, activation of T cells led to low-level expression of IL-4R, with IL-4 itself up-regulating IL-4R, especially in CD4 cells. The majority of chronic lymphocytic leukaemia samples were positive for IL-4R expression, whilst most other leukemic samples were negative.

  18. Gammaherpesvirus-driven plasma cell differentiation regulates virus reactivation from latently infected B lymphocytes.

    Directory of Open Access Journals (Sweden)

    Xiaozhen Liang

    2009-11-01

    Full Text Available Gammaherpesviruses chronically infect their host and are tightly associated with the development of lymphoproliferative diseases and lymphomas, as well as several other types of cancer. Mechanisms involved in maintaining chronic gammaherpesvirus infections are poorly understood and, in particular, little is known about the mechanisms involved in controlling gammaherpesvirus reactivation from latently infected B cells in vivo. Recent evidence has linked plasma cell differentiation with reactivation of the human gammaherpesviruses EBV and KSHV through induction of the immediate-early viral transcriptional activators by the plasma cell-specific transcription factor XBP-1s. We now extend those findings to document a role for a gammaherpesvirus gene product in regulating plasma cell differentiation and thus virus reactivation. We have previously shown that the murine gammaherpesvirus 68 (MHV68 gene product M2 is dispensable for virus replication in permissive cells, but plays a critical role in virus reactivation from latently infected B cells. Here we show that in mice infected with wild type MHV68, virus infected plasma cells (ca. 8% of virus infected splenocytes at the peak of viral latency account for the majority of reactivation observed upon explant of splenocytes. In contrast, there is an absence of virus infected plasma cells at the peak of latency in mice infected with a M2 null MHV68. Furthermore, we show that the M2 protein can drive plasma cell differentiation in a B lymphoma cell line in the absence of any other MHV68 gene products. Thus, the role of M2 in MHV68 reactivation can be attributed to its ability to manipulate plasma cell differentiation, providing a novel viral strategy to regulate gammaherpesvirus reactivation from latently infected B cells. We postulate that M2 represents a new class of herpesvirus gene products (reactivation conditioners that do not directly participate in virus replication, but rather facilitate virus reactivation by manipulating the cellular milieu to provide a reactivation competent environment.

  19. Classical scrapie prions in ovine blood are associated with B lymphocytes and platelets-rich plasma

    Science.gov (United States)

    Classical scrapie is a naturally occurring fatal brain disease of sheep and goats which is caused by prions, a novel class of infectious agent, and is accompanied by the accumulation of abnormal isoforms of prion protein (PrP-Sc) in certain neural and lymphoid tissues. Although collection of a blood...

  20. 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

  1. The association between DRESS and the diminished numbers of peripheral B lymphocytes and natural killer cells.

    Science.gov (United States)

    Yazicioglu, Mehtap; Elmas, Reyhan; Turgut, Burhan; Genchallac, Tugba

    2012-05-01

    Drug reaction with eosinophilia and systemic symptoms (DRESS) is a drug-induced, severe multiorgan system reaction whose exact pathogenesis remains unknown. This study aimed at evaluating specific changes in peripheral blood lymphocyte subtypes associated with DRESS during antibiotic treatment. We analyzed six patients with DRESS. A complete blood count and peripheral blood lymphocytes immunophenotyping were carried out at symptom onset and at follow-up visits. Acute-phase reactants and liver enzymes were measured in all patients. Other tests - viral serology, serum immunoglobulin levels, and skin tests were performed when possible. B-cell counts were low in all patients at the onset of DRESS, and natural killer (NK) cells were low in all cases except one. During recovery, B-cell numbers were within a normal range in five patients. In one, there was even a 10-fold increase in B-cell counts, although the level was mildly low after 3 months. NK-cell numbers were within a normal range in three patients. The mean numbers of B cells and NK cells were significantly higher in the second samples compared to the values on admission. Serum IgA and IgM levels were low in one patient. The drug provocation test was positive with cefotaxime in one patient. Viral serology, performed on five patients, was negative. A decrease in B-cell and NK-cell counts was the most consistent finding associated with the onset of antibiotic-induced DRESS in our patients. This immunologic alteration might be a useful predictor of DRESS development.

  2. Human severe combined immunodeficiency disease: phenotypic and functional characteristics of peripheral B lymphocytes.

    Science.gov (United States)

    Gougeon, M L; Drean, G; Le Deist, F; Dousseau, M; Fevrier, M; Diu, A; Theze, J; Griscelli, C; Fischer, A

    1990-11-01

    Human severe combined immunodeficiency disease (SCID) includes an X-chromosome-linked type characterized by a complete absence of mature T cells, hypogammaglobulinemia but normal or elevated number of B cells, suggesting that the disease results from a block in early T cell differentiation. It has been shown that B cells from obligate carrier women of this disorder exhibit the preferential use of the nonmutant X chromosome as the active X (as shown for T cells), suggesting that the SCID gene product has a direct effect on B cells as well as on T cells. To examine this question, we analyzed the phenotypic and functional characteristics of peripheral B cells from nine infants with SCID. We found a constant absence of spontaneously expressed activation Ag on B cell membrane from all SCID patients tested which contrasts with the phenotypic pattern exhibited by age-matched infants whom all cells bearing surface Ig express the 4F2 Ag and to a lesser extent the transferrin receptor. Concurrently, B cells from SCID patients have a profound impairment in their responses to stimuli that induce in vitro B cell proliferation and differentiation. Although rIL-2 and low-Mr B cell growth factor are potent inducers of proliferation on age-matched infants' B cells, they are poorly efficient in inducing proliferation of anti-mu-activated SCID B cells. This impairment is not related to the resting B cell phenotype of SCID B cells as shown by comparison with normal resting B cells. Furthermore, we observed an apparent block in B cell differentiation inasmuch as neither rIL-2 nor rIL-6 could support SAC-activated SCID B cell differentiation, both lymphokines being very efficient in inducing SAC-activated age-matched infants' B cell or purified resting B cell differentiation. These results suggest that the SCID gene defect has a direct effect on B cells and is required during B cell maturation.

  3. Inherited predisposition to CLL is detectable as subclinical monoclonal B-lymphocyte expansion.

    Science.gov (United States)

    Rawstron, Andy C; Yuille, Martin R; Fuller, Julie; Cullen, Matthew; Kennedy, Ben; Richards, Stephen J; Jack, Andrew S; Matutes, Estella; Catovsky, Daniel; Hillmen, Peter; Houlston, Richard S

    2002-10-01

    Monoclonal chronic lymphocytic leukemia (CLL)-phenotype cells are detectable in 3.5% of otherwise healthy persons using flow cytometric analysis of CD5/CD20/CD79b expression on CD19-gated B cells. To determine whether detection of such CLL-phenotype cells is indicative of an inherited predisposition, we examined 59 healthy, first-degree relatives of patients from 21 families with CLL. CLL-phenotype cells were detected in 8 of 59 (13.5%) relatives, representing a highly significant increase in risk (P =.00002). CLL-phenotype cell levels were stable with time and had the characteristics of indolent CLL. Indolent and aggressive clinical forms were found in family members, suggesting that initiation and proliferation involves distinct factors. The detection of CLL-phenotype cells provides a surrogate marker of carrier status, potentially facilitating gene identification through mapping in families and direct analysis of isolated CLL-phenotype cells.

  4. Regulatory B lymphocyte functions should be considered in chronic lymphocytic leukemia.

    Science.gov (United States)

    Mohr, Audrey; Renaudineau, Yves; Bagacean, Cristina; Pers, Jacques-Olivier; Jamin, Christophe; Bordron, Anne

    2016-05-01

    Chronic lymphocytic leukemia (CLL) is characterized by an abnormal expansion of mature B cells in the bone marrow and their accumulation in blood and secondary lymphoid organs. Tumor CLL cells share expression of various surface molecules with many subsets of B cells and have several common characteristics with regulatory B cells (B regs). However, the identification of B regs and their role in CLL remain elusive. The aim of this review is to summarize recent works regarding the regulatory and phenotypic characteristic of B regs and their associated effects on the immune system. It is also meant to highlight their potential importance with regards to the immunotherapeutic response.

  5. Fetal Hematopoietic Stem Cell Transplantation Fails to Fully Regenerate the B-Lymphocyte Compartment.

    Science.gov (United States)

    Ghosn, Eliver Eid Bou; Waters, Jeffrey; Phillips, Megan; Yamamoto, Ryo; Long, Brian R; Yang, Yang; Gerstein, Rachel; Stoddart, Cheryl A; Nakauchi, Hiromitsu; Herzenberg, Leonore A

    2016-01-12

    B cells are key components of cellular and humoral immunity and, like all lymphocytes, are thought to originate and renew from hematopoietic stem cells (HSCs). However, our recent single-HSC transfer studies demonstrate that adult bone marrow HSCs do not regenerate B-1a, a subset of tissue B cells required for protection against pneumonia, influenza, and other infections. Since B-1a are regenerated by transfers of fetal liver, the question arises as to whether B-1a derive from fetal, but not adult, HSCs. Here we show that, similar to adult HSCs, fetal HSCs selectively fail to regenerate B-1a. We also show that, in humanized mice, human fetal liver regenerates tissue B cells that are phenotypically similar to murine B-1a, raising the question of whether human HSC transplantation, the mainstay of such models, is sufficient to regenerate human B-1a. Thus, our studies overtly challenge the current paradigm that HSCs give rise to all components of the immune system.

  6. Gpr97 is essential for the follicular versus marginal zone B-lymphocyte fate decision.

    Science.gov (United States)

    Wang, J-J; Zhang, L-L; Zhang, Hong-x; Shen, C-L; Lu, S-y; Kuang, Y; Wan, Y-h; Wang, W-g; Yan, H-m; Dang, S-y; Fei, J; Jin, X-l; Wang, Z-g

    2013-10-10

    Gpr97 is an orphan adhesion GPCR and is highly conserved among species. Up to now, its physiological function remains largely unknown. Here, we show that Gpr97 deficiency results in an extensive reduction in B220(+) lymphocytes in mice. More intensive analyses reveal an expanded marginal zone but a decreased follicular B-cell population in Gpr97(-/-)spleen, which displays disorganized architecture characterized by diffuse, irregular B-cell areas and the absence of discrete perifollicular marginal and mantle zones. In vivo functional studies reveal that the mutant mice could generate antibody responses to T cell-dependent and independent antigens, albeit enhanced response to the former and weakened response to the latter. By screening for the molecular events involved in the observed phenotypes, we found that lambda 5 expression is downregulated and its upstream inhibitor Aiolos is increased in the spleen of mutant mice, accompanied by significantly enhanced phosphorylation and nuclear translocation of cAMP response element-binding protein. Interestingly, increased constitutive Nf-κb p50/p65 expression and activity were observed in Gpr97(-/-) spleen, implicating a crucial role of Gpr97 in regulating Nf-κb activity. These findings uncover a novel biological function of Gpr97 in regulating B-cell development, implying Gpr97 as a potential therapeutic target for treatment of immunological disorders.

  7. Mutations, kataegis, and translocations in B lymphocytes: towards a mechanistic understanding of AID promiscuous activity

    Science.gov (United States)

    Casellas, Rafael; Basu, Uttiya; Yewdell, William T.; Chaudhuri, Jayanta; Robbiani, Davide F.; Di Noia, Javier M.

    2016-01-01

    As B cells engage in the immune response they express the deaminase AID to initiate the hypermutation and recombination of immunoglobulin genes, which are crucial processes for the efficient recognition and disposal of pathogens, However, AID must be tightly controlled in B cells to minimize off-targeting mutations, which can drive chromosomal translocations and the development of B cell malignancies, such as lymphomas. Recent genomic and biochemical analyses have begun to unravel the crucial question of how AID-mediated deamination is targeted outside immunoglobulin genes. Here, we discuss the transcriptional and topological features that are emerging as key drivers of AID promiscuous activity. PMID:26898111

  8. 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

    2012-01-01

    Protein A (SpA) of Staphylococcus aureus is known to target the paratope of immunoglobulins expressing VH3 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. PMID:22367177

  9. [B lymphocyte stimulator (BLyS/BAFF) level in sera of patients with lupus].

    Science.gov (United States)

    Mercado, Ulises; Díaz-Molina, Raúl

    2016-01-01

    Introducción: el estimulador de linfocitos B (BLyS/BAFF) es una proteína endógena fundamental en la diferenciación y la maduración de linfocitos B. En el lupus se han encontrado niveles altos de BLyS. Métodos: se analizaron muestras séricas de 92 pacientes con lupus (94 % mujeres, con una mediana de edad de 35.5) y 106 controles (50 donadores de sangre, 38 pacientes con artritis reumatoide y 18 pacientes con esclerodermia). El punto de corte de BLyS ˃ 1.98 ng/mL corresponde al percentil 95 de los 50 donadores de sangre. También se evaluaron anticuerpos contra ADN nativo y actividad de enfermedad. Durante el seguimiento, los niveles de BLyS en 32 pacientes mostraron heterogeneidad. Resultados: la mediana de BLyS en 92 pacientes con lupus fue de 1.9 ng/mL (rango 0.4-5.3), comparada con 1.30, 1.35, y 1.35 ng/mL en donadores de sangre, pacientes con artritis reumatoide y pacientes con esclerodermia, respectivamente. Treinta y nueve pacientes con lupus tuvieron niveles elevados de BLyS (mediana 2.8 ng/mL), comparados con el grupo control. Hubo una moderada correlación entre títulos de anti-ADN (r = 0.34) y actividad de enfermedad (0.45). El seguimiento de 32 pacientes mostró un nivel de BLyS persistentemente elevado, normal o con variaciones intermitentes. Conclusión: el nivel de BLyS resultó elevado en algunos pacientes con lupus. Hubo una moderada correlación con títulos de anti-ADN y actividad de enfermedad. El seguimiento de 32 pacientes mostró fluctuaciones en los niveles de BLyS.

  10. Crosstalk between B lymphocytes, microbiota and the intestinal epithelium governs immunity versus metabolism in the gut

    Science.gov (United States)

    Shulzhenko, Natalia; Morgun, Andrey; Hsiao, William; Battle, Michele; Yao, Michael; Gavrilova, Oksana; Orandle, Marlene; Mayer, Lloyd; Macpherson, Andrew J; McCoy, Kathy D; Fraser-Liggett, Claire; Matzinger, Polly

    2014-01-01

    Using a systems biology approach, we discovered and dissected a three-way interaction between the immune system, the intestinal epithelium and the microbiota. We found that, in the absence of B cells, or of IgA, and in the presence of the microbiota, the intestinal epithelium launches its own protective mechanisms, upregulating interferon-inducible immune response pathways and simultaneously repressing Gata4-related metabolic functions. This shift in intestinal function leads to lipid malabsorption and decreased deposition of body fat. Network analysis revealed the presence of two interconnected epithelial-cell gene networks, one governing lipid metabolism and another regulating immunity, that were inversely expressed. Gene expression patterns in gut biopsies from individuals with common variable immunodeficiency or with HIV that also have intestinal malabsorption were very similar to those of the B cell–deficient mice, providing a possible explanation for a longstanding enigmatic association between immunodeficiency and defective lipid absorption in humans. PMID:22101768

  11. Studying the replication history of human B lymphocytes by real-time quantitative (RQ)-PCR.

    Science.gov (United States)

    van Zelm, Menno C; Berkowska, Magdalena A; van Dongen, Jacques J M

    2013-01-01

    The cells of the adaptive immune system, B and T lymphocytes, each generate a unique antigen receptor through V(D)J recombination of their immunoglobulin (Ig) and T cell receptor (TCR) loci, respectively. Such rearrangements join coding elements to form a coding joint and delete the intervening DNA as circular excision products containing the signal joint. These excision circles are stable structures that cannot replicate and have no function in the cell. Since the coding joint in the genome is replicated with each cell division, the ratio between coding joints and signal joints in a population of B cells can be used as a measure for proliferation. This chapter describes a real-time quantitative (RQ-)PCR-based approach to quantify proliferation through calculating the ratio between coding joints and signal joints of the frequently occurring intronRSS-Kde rearrangements in the IGK light chain locus. The approach is useful to study basic B-cell biology as well as abnormal proliferation in human diseases.

  12. The distinctive germinal center phase of IgE+ B lymphocytes limits their contribution to the classical memory response

    Science.gov (United States)

    The mechanisms involved in the maintenance of memory IgE responses are poorly understood, and the role played by germinal center (GC) IgE+ cells in memory responses is particularly unclear. IgE B cell differentiation is characterized by a transient GC phase, a bias towards the plasma cell (PC) fate,...

  13. 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, Anders Jørgen; 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...

  14. B-lymphocyte subpopulations are equally susceptible to Epstein-Barr virus infection, irrespective of immunoglobulin isotype expression.

    Science.gov (United States)

    Ehlin-Henriksson, Barbro; Gordon, John; Klein, George

    2003-04-01

    While Epstein-Barr virus (EBV) is known to establish latency in the memory B-cell compartment, there is controversy as to whether the memory or the naïve B cell is the initial target for infection. Here we have explored the infectability of the B-cell subsets contained in peripheral blood and tonsils, as distinguished by their surface expression of the immunoglobulin isotypes that help to define naïve and memory pools. First we show that both CD21 and major histocompatibility complex (MHC) class II molecules--respectively, the major receptor and co-receptor for EBV on B cells--are expressed at similar levels on blood and tonsillar B cells, irrespective of surface immunoglobulin class, indicating that each of the subsets demonstrate an equal potential, at least for infection. Then, following in vitro infection of total tonsillar B cells, we found that the relative frequencies of immunoglobulin (Ig)M-, IgG- and IgA-positive cells containing EBV-encoded Epstein-Barr virus nuclear antigen 5 (EBNA5) protein at 48 hr were similar to those of the starting population. However, IgD expression was uniformly decreased, probably as a consequence of cellular activation. These data indicate that recirculating B cells have both the potential for, and susceptibility to, initial infection by EBV, irrespective of the immunoglobulin isotype expressed.

  15. CLONAL CHRONIC LYMPHOCYTIC LEUKEMIA-LIKE B-LYMPHOCYTES IN THE BLOOD OF PATIENTS WITH CUTANEOUS T-CELL DISORDERS

    NARCIS (Netherlands)

    DAENEN, S; VADER, PCV; BLOM, N; PIETENS, J; HOLLEMA, H; SMIT, JW

    1993-01-01

    A population of B cells with characteristics of chronic lymphocytic leukaemia was found in the peripheral blood of four patients who presented with cutaneous infiltration of atypical CD4+ T cells with cerebriform nuclei. The B cells had a low density of immunoglobulin on their surface membrane, expr

  16. B lymphocytes induce the formation of follicular dendritic cell clusters in a lymphotoxin alpha-dependent fashion.

    Science.gov (United States)

    Fu, Y X; Huang, G; Wang, Y; Chaplin, D D

    1998-04-06

    Lymphotoxin (LT)alpha is expressed by activated T cells, especially CD4(+) T helper type 1 cells, and by activated B and natural killer cells, but the functions of this molecule in vivo are incompletely defined. We have previously shown that follicular dendritic cell (FDC) clusters and germinal centers (GCs) are absent from the peripheral lymphoid tissues of LTalpha-deficient (LTalpha-/-) mice. LTalpha-/- mice produce high levels of antigen-specific immunoglobulin (Ig)M, but very low levels of IgG after immunization with sheep red blood cells. We show here that LTalpha-expressing B cells are essential for the recovery of primary, secondary, and memory humoral immune responses in LTalpha-/- mice. It is not necessary for T cells to express LTalpha to support these immune functions. Importantly, LTalpha-expressing B cells alone are essential and sufficient for the formation of FDC clusters. Once these clusters are formed by LTalpha-expressing B cells, then LTalpha-deficient T cells can interact with B cells to generate GCs and productive class-switched antibody responses. Thus, B cells themselves provide an essential signal that induces and maintains the lymphoid microenvironment essential for GC formation and class-switched Ig responses.

  17. Enhancement of terminal B lymphocyte differentiation in vitro by fibroblast-like stromal cells from human spleen.

    Science.gov (United States)

    Skibinski, G; Skibinska, A; Stewart, G D; James, K

    1998-12-01

    Stromal elements are major components of lymphoid tissues contributing to both tissue architecture and function. In this study we report on the phenotype and function of fibroblast-like stromal cells obtained from human spleen. These cells express high levels of CD44 and ICAM-1 and moderate levels of VLA-4, VCAM, CD40 and CD21. They fail to express endothelial, epithelial, lymphocyte and monocyte/macrophage markers. We show that these cells interact with B cell blasts induced in vitro by anti-CD40 and anti-mu stimulation. As a result of these interactions both IL-6 and IgG secretion into culture medium is increased. The enhanced secretion of IgG is partly inhibited by abolishing B cell blaststromal cell contact or by anti-IL-6, anti-VCAM or anti-CD49d antibodies. Our studies also suggest that the ability of stromal cells to promote B cell survival is most likely the underlying mechanism of the enhanced immunoglobulin secretion. Comparison of stromal cells from different lymphoid and non-lymphoid organs revealed that bone marrow- and spleen-derived stromal cells are the most effective in promoting B cell blast differentiation.

  18. 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.

  19. 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 n...

  20. Ex vivo analysis of human memory B lymphocytes specific for A and B influenza hemagglutinin by polychromatic flow-cytometry.

    Directory of Open Access Journals (Sweden)

    Monia Bardelli

    Full Text Available Understanding the impact that human memory B-cells (MBC, primed by previous infections or vaccination, exert on neutralizing antibody responses against drifted influenza hemagglutinin (HA is key to design best protective vaccines. A major obstacle to these studies is the lack of practical tools to analyze HA-specific MBCs in human PBMCs ex vivo. We report here an efficient method to identify MBCs carrying HA-specific BCR in frozen PBMC samples. By using fluorochrome-tagged recombinant HA baits, and vaccine antigens from mismatched influenza strains to block BCR-independent binding, we developed a protocol suitable for quantitative, functional and molecular analysis of single MBCs specific for HA from up to two different influenza strains in the same tube. This approach will permit to identify the naive and MBC precursors of plasmablasts and novel MBCs appearing in the blood following infection or vaccination, thus clarifying the actual contribution of pre-existing MBCs in antibody responses against novel influenza viruses. Finally, this protocol can allow applying high throughput deep sequencing to analyze changes in the repertoire of HA⁺ B-cells in longitudinal samples from large cohorts of vaccinees and infected subjects with the ultimate goal of understanding the in vivo B-cell dynamics driving the evolution of broadly cross-protective antibody responses.

  1. Mite allergen Der-p2 triggers human B lymphocyte activation and Toll-like receptor-4 induction.

    Directory of Open Access Journals (Sweden)

    Jaw Ji Tsai

    Full Text Available BACKGROUND: Allergic disease can be characterized as manifestations of an exaggerated inflammatory response to environmental allergens triggers. Mite allergen Der-p2 is one of the major allergens of the house dust mite, which contributes to TLR4 expression and function in B cells in allergic patients. However, the precise mechanisms of Der-p2 on B cells remain obscure. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the effects of Der-p2 on proinflammatory cytokines responses and Toll-like receptor-4 (TLR4-related signaling in human B cells activation. We demonstrated that Der-p2 activates pro-inflammatory cytokines, TLR4 and its co-receptor MD2. ERK inhibitor PD98059 significantly enhanced TLR4/MD2 expression in Der-p2-treated B cells. Der-p2 markedly activated mitogen-activated protein kinase (MAPK phosphatase-1 (MKP-1 and decreased p38 phosphorylation in B cells. MKP-1-siRNA downregulated TLR4/MD2 expression in Der-p2-treated B cells. In addition, Der-p2 significantly up-regulated expression of co-stimulatory molecules and increased B cell proliferation. Neutralizing Der-p2 antibody could effectively abrogate the Der-p2-induced B cell proliferation. Der-p2 could also markedly induce NF-κB activation in B cells, which could be counteracted by dexamethasone. CONCLUSIONS/SIGNIFICANCE: These results strongly suggest that Der-p2 is capable of triggering B cell activation and MKP-1-activated p38/MAPK dephosphorylation-regulated TLR4 induction, which subsequently enhances host immune, defense responses and development of effective allergic disease therapeutics in B cells.

  2. 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...... 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......SC peaked early (day 7) had higher prevaccination anti-DT levels than those who peaked later (P less than 0.05). In contrast, the prevaccination levels of anti-PRP did not correlate significantly with the magnitude of the antibody or AbSC response and did not affect the kinetics of the AbSC. Following...

  3. Regulation of B lymphocytes and plasma cells by innate immune mechanisms and stromal cells in rheumatoid arthritis.

    Science.gov (United States)

    Maseda, Damian; Bonami, Rachel H; Crofford, Leslie J

    2014-06-01

    B cells mediate multiple functions that influence immune and inflammatory responses in rheumatoid arthritis. Production of a diverse array of autoantibodies can happen at different stages of the disease, and are important markers of disease outcome. In turn, the magnitude and quality of acquired humoral immune responses is strongly dependent on signals delivered by innate immune cells. Additionally, the milieu of cells and chemokines that constitute a niche for plasma cells rely strongly on signals provided by stromal cells at different anatomical locations and times. The chronic inflammatory state therefore importantly impacts the developing humoral immune response and its intensity and specificity. We focus this review on B cell biology and the role of the innate immune system in the development of autoimmunity in patients with rheumatoid arthritis.

  4. 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.

  5. 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

    cytotoxic response causing tumor regression or remission in human blood cancer patients. Substituting rapamycin with mTOR kinase inhibitors that block both...Akt poly- peptide . EMBO J. 2010;29(23):3939-3951. 27. Lazorchak AS, Liu D, Facchinetti V, et al. Sin1- mTORC2 suppresses rag and il7r gene expres

  6. 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

  7. Construction and characterization of monoclonal antibodies against the extracellular domain of B-lymphocyte antigen CD20 using DNA immunization method.

    Science.gov (United States)

    Khademi, Fatemeh; Mostafaie, Ali; Parvaneh, Shahram; Gholami Rad, Farah; Mohammadi, Pantea; Bahrami, Gholamreza

    2017-02-01

    To date, several new anti-CD20 monoclonal antibodies (mAbs) have been developed for potential efficacies compared with familiar mAb rituximab. Despite the recent advances in development of anti-CD20 mAbs for the treatment of B cell malignancies, the efforts should be continued to develop novel antibodies with improved properties. However, the development of mAbs against CD20 as a multi-transmembrane protein is challenging due to the difficulty of providing a lipid environment that can maintain native epitopes. To overcome this limitation, we describe a simple and efficient DNA immunization strategy for the construction of a novel anti-CD20 mAb with improved anti-tumour properties. Using a DNA immunization strategy that includes intradermal (i.d.) immunization with naked plasmid DNA encoding the CD20 gene, we generated the hybridoma cell line D4, which secretes functional mAbs against an extracellular epitope of CD20. Immunocytochemistry analysis and a cell-based enzyme-linked immunosorbent assay using a Burkitt's lymphoma cell line showed that D4 mAbs are capable of binding to native extracellular epitopes of CD20. Moreover, the binding specificity of D4 mAbs was determined by western blot analysis. Cell proliferation was examined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Apoptosis was detected by the annexin V/propidium iodide staining and dye exclusion assay. The results showed that D4 anti-CD20 mAbs produced by DNA immunization exhibit potent growth inhibitory activity and have superior direct B-cell cytotoxicity compared to rituximab. We propose that antibody-induced apoptosis is one of the mechanisms of cell growth inhibition. Taken together, the data reported here open the path to DNA-based immunization for generating pharmacologically active monoclonal antibodies against CD20. In addition, the data support future in vivo animal testing and subsequent procedures to produce a potential therapeutic mAb.

  8. CD4 binding to major histocompatibility complex class II antigens induces LFA-1-dependent and -independent homotypic adhesion of B lymphocytes.

    Science.gov (United States)

    Kansas, G S; Cambier, J C; Tedder, T F

    1992-01-01

    T helper cells recognize processed antigen (Ag) in the context of major histocompatibility complex (MHC) class II antigens present on the surface of B cells and other Ag-presenting cells. This interaction is mediated through the T cell receptor complex with associate recognition of class II molecules by the CD4 molecule. In this study, the binding of a soluble recombinant CD4/Ig heavy chain fusion protein (CD4-gamma 3) or monoclonal antibody (mAb) to class II antigens on human B cells was shown to induce rapid and specific homotypic adhesion of B cells and most B lymphoblastoid cell lines. mAb reactive with CD4 inhibited CD4-gamma 3-induced adhesion and a mutant B lymphoblastoid cell line deficient in class II antigens failed to respond. Induction of homotypic adhesion was dependent on energy metabolism and a functional cytoskeleton, and class II+ pre-B cells did not exhibit adhesion in response to these stimuli, suggesting that cross-linking of class II molecules generated a transmembrane signal and did not simply aggregate cells. In addition, MHC class II-induced adhesion was Fc receptor independent, as 15 mAb of different Ig isotypes reactive with HLA-D or HLA-DQ gene products induced adhesion. Anti-class II mAb and CD4-gamma 3 were able to induce adhesion at concentrations as low as 10 ng/ml and 100 ng/ml, respectively. Suboptimal stimulation of B cell lines through HLA-D antigens induced homotypic adhesion that was dependent on the activation of LFA-1 (CD11a/CD18), and which could be blocked by specific mAb. However, at greater signal strengths, adhesion was not blocked by mAb against the known adhesion receptors, suggesting the induction of a novel adhesion pathway. Consistent with this, homotypic adhesion induced by engagement of MHC class II antigens was observed with LFA-1-deficient B cell lines, and was independent of CD49d or CD18 expression. Thus, the direct engagement of B cell class II antigens by CD4 is likely to generate transmembrane signals which trigger both LFA-1-dependent and LFA-1-independent adhesion pathways.

  9. Protein kinase D1/2 is involved in the maturation of multivesicular bodies and secretion of exosomes in T and B lymphocytes.

    Science.gov (United States)

    Mazzeo, C; Calvo, V; Alonso, R; Mérida, I; Izquierdo, M

    2016-01-01

    Multivesicular bodies (MVBs) are endocytic compartments that enclose intraluminal vesicles (ILVs) formed by inward budding from the limiting membrane of endosomes. In T lymphocytes, these ILV contain Fas ligand (FasL) and are secreted as 'lethal exosomes' following activation-induced fusion of the MVB with the plasma membrane. Diacylglycerol (DAG) and diacylglycerol kinase α (DGKα) regulate MVB maturation and polarized traffic, as well as subsequent secretion of pro-apoptotic exosomes, but the molecular basis underlying these phenomena remains unclear. Here we identify protein kinase D (PKD) family members as DAG effectors involved in MVB genesis and secretion. We show that the inducible secretion of exosomes is enhanced when a constitutively active PKD1 mutant is expressed in T lymphocytes, whereas exosome secretion is impaired in PKD2-deficient mouse T lymphoblasts and in PKD1/3-null B cells. Analysis of PKD2-deficient T lymphoblasts showed the presence of large, immature MVB-like vesicles and demonstrated defects in cytotoxic activity and in activation-induced cell death. Using pharmacological and genetic tools, we show that DGKα regulates PKD1/2 subcellular localization and activation. Our studies demonstrate that PKD1/2 is a key regulator of MVB maturation and exosome secretion, and constitutes a mediator of the DGKα effect on MVB secretory traffic.

  10. Rac1/p21-activated kinase pathway controls retinoblastoma protein phosphorylation and E2F transcription factor activation in B lymphocytes.

    Science.gov (United States)

    Zaldua, Natalia; Llavero, Francisco; Artaso, Alain; Gálvez, Patricia; Lacerda, Hadriano M; Parada, Luis A; Zugaza, José L

    2016-02-01

    Small GTPases of the Ras superfamily are capable of activating E2F-dependent transcription leading to cell proliferation, but the molecular mechanisms are poorly understood. In this study, using immortalized chicken DT40 B cell lines to investigate the role of the Vav/Rac signalling cascade on B cell proliferation, it is shown that the proliferative response triggered by B cell receptor activation is dramatically reduced in the absence of Vav3 expression. Analysis of this proliferative defect shows that in the absence of Vav3 expression, retinoblastoma protein (RB) phosphorylation and the subsequent E2F activation do not take place. By combining pharmacological and genetic approaches, phosphatidylinositol-3-kinase and phospholipase Cγ2 (PLCγ2) were identified as the key regulatory signalling molecules upstream of the Vav3/Rac pathway leading to RB phosphorylation and E2F transcription factor activation. Additionally, vav3(-/-) and plcγ2(-/-) DT40 B cells were not able to activate the RB-E2F complex wild-type phenotype when these genetically modified cells were transfected with constitutively active forms of RhoA or Cdc42. However, when these knockout cells were transfected with different constitutively active versions of PLCγ, Vav or Rac1, not only activation of the RB-E2F complex wild-type phenotype was recovered but also the cellular proliferation. Furthermore, by evaluating the effect of two known effector mutants of Rac1 (Rac1(Q61L/F37A) and Rac1(Q61L/Y40C) ), the RB-E2F complex activation dependency on p21-activated kinase (PAK) and protein kinase Cε (PKCε) activities was established, being independent of both actin cytoskeleton reorganization and Ras activity. These results suggest that PAK1 and PKCε may be potential therapeutic targets to stop uncontrolled B cell proliferation mediated by the Vav/Rac pathway.

  11. In vitro and in vivo analyses of a genetically—restricted antigen specific factor from mixed cell cultures of macrophage,T and B lymphocytes

    Institute of Scientific and Technical Information of China (English)

    CHAURMW; LAUASK

    1990-01-01

    An immunostimulatory factor was identified to be secreted by antigen-pulsed macrophages.This factor was able to induce the generation of antigen specific T helper lymphocytes in vitro as well as in vivo.Further in vitro experiments testing for the genetic restriction of this factor indicated that it is a geneticallyrestricted antigen specific factor (ASF).The Cunningham plaque assay was used to quantify the generation of T helper lymphocytes by measuring the number of plaque forming cells after sequential incubations of antigen-qulsed macrophages with T lymphocytes,and then spleen cells,and finally the TNP-coated sheep red blood cells.

  12. Abortive lytic Epstein–Barr virus replication in tonsil-B lymphocytes in infectious mononucleosis and a subset of the chronic fatigue syndrome

    Directory of Open Access Journals (Sweden)

    Lerner AM

    2012-11-01

    Full Text Available A Martin Lerner,1 Safedin Beqaj21Department of Medicine, Oakland University William Beaumont School of Medicine, Rochester, MI, USA; 2Pathology Inc, Torrance, CA, USAAbstract: A systematic 2001–2007 review of 142 chronic fatigue syndrome (CFS patients identified 106 CFS patients with elevated serum IgG antibodies to the herpesviruses Epstein–Barr virus (EBV, cytomegalovirus, or human herpesvirus (HHV 6 in single or multiple infections, with no other co-infections detected. We named these 106 patients group-A CFS. Eighty-six of these 106 group-A CFS patients (81% had elevated EBV early antibody, early antigen (diffuse, serum titers. A small group of six patients in the group-A EBV subset of CFS, additionally, had repetitive elevated-serum titers of antibody to the early lytic replication-encoded proteins, EBV dUTPase, and EBV DNA polymerase. The presence of these serum antibodies to EBV dUTPase and EBV DNA polymerase indicated EBV abortive lytic replication in these 6 CFS patients. None of 20 random control people (age- and sex-matched, with blood drawn at a commercial laboratory had elevated serum titers of antibody to EBV dUTPase or EBV DNA polymerase (P < 0.01. This finding needs verification in a larger group of EBV CFS subset patients, but if corroborated, it may represent a molecular marker for diagnosing the EBV subset of CFS. We review evidence that EBV abortive lytic replication with unassembled viral proteins in the blood may be the same in infectious mononucleosis (IM and a subset of CFS. EBV-abortive lytic replication in tonsil plasma cells is dominant in IM. No complete lytic virion is in the blood of IM or CFS patients. Complications of CFS and IM include cardiomyopathy and encephalopathy. Circulating abortive lytic-encoded EBV proteins (eg, EBV dUTPase, EBV DNA polymerase, and others may be common to IM and CFS. The intensity and duration of the circulating EBV-encoded proteins might differentiate the IM and EBV subsets of CFS. Abortive lytic replication may be a pathogenic mechanism for EBV disease. EBV (HHV4 is a gamma herpesvirus composed of dsDNA about 170 Kb in length. For this discussion, there are early genes (including expressions of encoded proteins EBV dUTPase, DNA polymerase, and nuclear proteins and late genes (including expressions of capsid and membrane proteins. Abortive infection infers incomplete virion expressions of either early or late proteins, but the virion is incomplete. The lytic virus infers a complete virion. The pathologic consequences of EBV abortive replication are currently being investigated by authors.Keywords: Epstein–Barr virus, chronic fatigue syndrome, subset chronic fatigue syndrome, abortive lytic replication

  13. Distinctive effects of the Epstein-Barr virus family of repeats on viral latent gene promoter activity and B-lymphocyte transformation.

    Science.gov (United States)

    Ali, Ahmed K M; Saito, Satoru; Shibata, Sachiko; Takada, Kenzo; Kanda, Teru

    2009-09-01

    The Epstein-Barr virus (EBV), a human B-lymphotropic gamma herpesvirus, contains multiple repetitive sequences within its genome. A group of repetitive sequences, known as the family of repeats (FR), contains multiple binding sites for the viral trans-acting protein EBNA-1. The FR sequences are important for viral genome maintenance and for the regulation of the promoter involved in viral latent gene expression. It has been reported that a palindromic sequence with a putative secondary structure exists at the 3' end of the FR in the genome of the EBV B95-8 strain and that this palindromic sequence has been deleted from the FR of the commonly used EBV miniplasmids. For the first time, we cloned an EBV B95-8 DNA fragment containing the full-length FR, which enabled us to examine the functional difference between full-length and deleted FRs. The full-length FR, like the deleted FR, functioned as a transcriptional enhancer of the viral latent gene promoter, but that transactivation was significantly attenuated in the case of the full-length FR. No significant enhancement of replication was observed when the deleted FR was replaced with the full-length FR in an EBV miniplasmid. By contrast, when the same set of FR sequences were tested in the context of the complete EBV genome, the full-length FR resulted in more-efficient B-cell transformation than the deleted FR. We propose that the presence of the full-length FR contributes to the precise regulation of the viral latent promoter and increases the efficiency of B-cell transformation.

  14. [Renal infiltrate by a plasmocytoïd chronic B lymphocytic leukaemia and renal failure: a rare occurrence in nephropathology. A case report and review of the literature].

    Science.gov (United States)

    Aymard, Bernadette; Beghoura, Rachid; Molina, Thierry Jo

    2011-11-01

    We report the case of a 55-year-old male with renal failure as the initial manifestation of interstitial and focal infiltration of the kidneys by a small B-cell lymphoma. Since three years, this patient had a history of CLL with plasmocytic differentiation and was left untreated owing to stade A Binet classification. After chemotherapy, the lymphocytosis and the adenopathies disappear and the renal function improve. Infiltration of the kidneys by non-Hodgkin small B-cell lymphoma, including chronic lymphocytic leukaemia (CLL), is usually asymptomatic, fortuitously discovered at the time of an X-ray examination or at autopsy. Association with renal failure is extremely rare. We review the reported cases of renal failure associated with lymphomatous infiltration (13 cases of CLL and five cases of lymphoplasmocytic lymphoma kappa or lambda IgM), with the following conclusions: in most cases, renal insufficiency appears in a few months and significantly disappears after chemotherapy; the renal infiltrate is usually focal in lymphoplasmocytic lymphoma and rather massive and diffuse in CLL; the neoplastic feature of a small B-cell lymphoïd infiltrate may be difficult to determine: a poorly limited, monomorphous, CD20+ CD5+ lymphoid infiltrate is lymphomatous. In case of plasmocytic differentiation, it must be looked for kappa or lambda monotypy; the type of the lymphomatous infiltrate according to the WHO 2008 classification may be difficult to determine in a small sampling of renal tissue: the renal infiltrate must be compared, if possible, with a lymph node infiltrate. Owing to its bad prognosis, mantle cell lymphoma must be distinguished from other small B-cell lymphoma like CLL/small lymphocytic lymphoma, marginal zone lymphoma and lymphoplasmocytic lymphoma.

  15. Soluble mediators can replace helper T cells in the activation of resting B lymphocytes: evidence for a human B cell activating factor.

    Science.gov (United States)

    Diu, A; Février, M; Moreau, J L; Gougeon, M L; Abadie, A; Thèze, J

    1988-01-01

    We were interested in studying the participation of T cell-derived soluble factors in the early steps of B cell activation. Thus supernatants containing such factors were obtained following activation of human T cell clones and their effects on isolated B cells investigated. These supernatants induced activation, blastogenesis and proliferation of purified resting human B cells. Our results strongly suggest the existence of a B cell Activating Factor (BCAF) of apparent molecular weight (m.w.) of 12,000-15,000 daltons which acts directly on resting B cells and replaces helper T cells in B cell activation.

  16. Effect of Leflunomide on the Abnormal Expression of Lipid Rafts and F-Actin in B Lymphocytes from Patients with Systemic Lupus Erythematosus

    Directory of Open Access Journals (Sweden)

    Guang Fu Dong

    2015-01-01

    Full Text Available Purposes. To investigate the possible changes in B cell subsets and in B cell expression patterns of lipid rafts (LRs and F-actin in patients with SLE and whether leflunomide treatment may have effect on these changes. Methods. The B cell subsets and LRs expression were determined by flow cytometry and confocal microscopy, and F-actin expression was examined by confocal microscopy. Results. CD27+IgD+ B cell subsets were significantly decreased while CD38+CD95+ B cell subsets increased in SLE patients. The LRs levels of B cells were remarkably increased and positively correlated with SLEDAI and anti-dsDNA titer in SLE patients. The expression level of LRs was significantly higher in CD38+ B cells than CD38− B cells and negatively correlated with C3 levels. The increased expression of LRs was associated with reduced expression of F-actin in the B cells from active SLE patients. Furthermore, in vitro treatment of the cells with A771726 reduced the expression level of LRs, attenuated the overaggregation of LRs, and normalized the distribution of F-actin. Conclusions. There were abnormalities in B cell subsets and LRs and F-actin expression of B cell from SLE patients. Modulation of B cell expression of LRs and F-actin by LEF could be a potential therapeutic target for SLE.

  17. Effects of prolactin on the proliferation of human B lymphocytes%催乳素对人B淋巴细胞增殖功能的影响

    Institute of Scientific and Technical Information of China (English)

    孙翔; 孙清河; 王辉

    2006-01-01

    目的探讨催乳素(PRL)对B淋巴细胞生长的调节作用.方法将生理浓度(10ng·ml-1)的PRL加到IM-9细胞中培养72h,以MTT比色分析法检测细胞增殖情况.结果空白对照组、脂多糖(LPS)组、PRL组、LPS+PRL组、LPS+溴隐停(Br)组、LPS+PRL+Br组A值分别为1.00±0.09、1.11±0.14、1.21±0.23、1.38±0.44、0.95±0.14、0.89±0.11.与空白对照组比较,PRL(t=2.689,P<0.01)、LPS(t=2.292,P<0.05)均能促进IM-9细胞的增殖;与LPS组相比,加入Br后对IM-9细胞的增殖有抑制作用(t=2.556,P<0.05);与LPS-PRL组相比,加入Br后对IM-9细胞的增殖亦有抑制作用(t=3.417,P<0.01).结论人PRL能明显地促进IM-9细胞的增殖,Br对IM-9细胞的增殖有抑制作用.

  18. CD40 signaling drives B lymphocytes into an intermediate memory-like state, poised between naïve and plasma cells.

    Science.gov (United States)

    Upadhyay, Mala; Priya, G Krishna; Ramesh, P; Madhavi, M B; Rath, Satyajit; Bal, Vineeta; George, Anna; Vaidya, Tushar

    2014-10-01

    Immunological memory comprising of antigen-specific B and T cells contributes to the acquisition of long-term resistance to pathogens. Interactions between CD40 on B cells and CD40L on T cells are responsible for several aspects of acquired immune responses including generation of memory B cells. In order to gain insights into events leading to memory B cell formation, we analyzed the genome-wide expression profile of murine naive B cells stimulated in the presence of anti-CD40. We have identified over 8,000 genes whose expression is altered minimally 1.5-fold at least at one time point over a 3-day time course. The array analysis indicates that changes in expression level of maximum number of these genes occur within 24 h of anti-CD40 treatment. In parallel, we have studied the events following CD40 ligation by examining the expression of known regulators of naive B cell to plasma cell transition, including Pax5 and BLIMP1. The expression profile of these regulatory genes indicates firstly, that CD40 signaling activates naïve B cells to a phenotype that is intermediate between the naive and plasma cell stages of the B cell differentiation. Secondly, the major known regulator of plasma cell differentiation, BLIMP1, gets irreversibly downregulated upon anti-CD40 treatment. Additionally, our data reveal that CD40 signaling mediated BLIMP1 downregulation occurs by non-Pax5/non-Bcl6 dependent mechanisms, indicating novel mechanisms at work that add to the complexity of understanding of B cell master regulatory molecules like BLIMP1 and Pax5.

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

    Institute of Scientific and Technical Information of China (English)

    Yi-Ning Yang; Xiao-Rui Wang; You-Wen Qin; Li-Ping Wan; Ying Jiang; Chun Wang

    2015-01-01

    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 lympho-blastic 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. Copyright © 2015, Chinese Medical Association Production. Production and hosting by Elsevier B.V. on behalf of KeAi Communications Co., Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

  20. The IgH 3′ regulatory region governs μ chain transcription in mature B lymphocytes and the B cell fate

    Science.gov (United States)

    Saintamand, Alexis; Rouaud, Pauline; Garot, Armand; Saad, Faten; Carrion, Claire; Oblet, Christelle; Cogné, Michel; Pinaud, Eric; Denizot, Yves

    2015-01-01

    We report that the IgH 3′ regulatory region (3′RR) has no role on μ chain transcription and pre-BCR expression in B cell progenitors. In contrast, analysis of heterozygous IgH aΔ3′RR/bwt mice indicated that the 3′RR controls μ chain transcripts in mature splenocytes and impacts membrane IgM density without obvious effect on BCR signals (colocalisation with lipid rafts and phosphorylation of Erk and Akt after BCR crosslinking). Deletion of the 3′RR modulates the B cell fate to less marginal zone B cells. In conclusion, the 3′RR is dispensable for pre-BCR expression and necessary for optimal commitments toward the marginal zone B cell fate. These results reinforce the concept of a dual regulation of the IgH locus transcription and accessibility by 5′ elements at immature B cell stages, and by the 3′RR as early as the resting mature B cell stage and then along further activation and differentiation. PMID:25742787

  1. Hepatitis C virus in human B lymphocytes transformed by Epstein-Barr virus in vitro by in situ reverse transcriptase-polymerase chain reaction

    Institute of Scientific and Technical Information of China (English)

    Ji Lin Cheng; Bao Ling Liu; Yi Zhang; Wen Bin Tong; Zheng Yan; Bai Fang Feng

    2001-01-01

    AIM To study persistence and replication ofheltitis C virus (HCV) in patients' peripheralblood mononuclear cells (PBMC) cultured invitro.METHODS Epstein-Barr virus (EBV) was usedto transform the hepatitis C virus from a HCVpositive patient to permanent lymphoblastoidcell lines (LCL). Positive and negative HCV RNAstrands of the cultured cells and growth mediawere detected by reverse transcriptase-polymerase chain reaction ( RT-PCR ) eachmonth. Core and NS5 proteins of HCV werefurther tested using immunohistochemical SPmethod and in situ RT-PCR.RESULTS HCV RNA positive strands wereconsistently detected the cultured cells for oneyear. The negative-strand RNA in LCL cells andthe positive-strand RNA in supernatants wereobserved intermittently. Immunohistochemicalresults medicated expression of HCV NS3 and Cproteins in LCL cytoplasm mostly. The positivesignal of PCR product was dark blue and mainlylocalized to the LCL cytoplasm. The RT-PCRsignal was eliminated by overnight RNasedigestion but not DNase digestion.CONCLUSION HCV may exist and remainfunctional in a cultured cell line for a longperiod.

  2. 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.

  3. CX3CR1 is expressed by human B lymphocytes and mediates [corrected] CX3CL1 driven chemotaxis of tonsil centrocytes.

    Directory of Open Access Journals (Sweden)

    Anna Corcione

    Full Text Available BACKGROUND: Fractalkine/CX(3CL1, a surface chemokine, binds to CX(3CR1 expressed by different lymphocyte subsets. Since CX(3CL1 has been detected in the germinal centres of secondary lymphoid tissue, in this study we have investigated CX(3CR1 expression and function in human naïve, germinal centre and memory B cells isolated from tonsil or peripheral blood. METHODOLOGY/PRINCIPAL FINDINGS: We demonstrate unambiguously that highly purified human B cells from tonsil and peripheral blood expressed CX(3CR1 at mRNA and protein levels as assessed by quantitative PCR, flow cytometry and competition binding assays. In particular, naïve, germinal centre and memory B cells expressed CX(3CR1 but only germinal centre B cells were attracted by soluble CX(3CL1 in a transwell assay. CX(3CL1 signalling in germinal centre B cells involved PI3K, Erk1/2, p38, and Src phosphorylation, as assessed by Western blot experiments. CX(3CR1(+ germinal centre B cells were devoid of centroblasts and enriched for centrocytes that migrated to soluble CX(3CL1. ELISA assay showed that soluble CX(3CL1 was secreted constitutively by follicular dendritic cells and T follicular helper cells, two cell populations homing in the germinal centre light zone as centrocytes. At variance with that observed in humans, soluble CX(3CL1 did not attract spleen B cells from wild type mice. OVA immunized CX(3CR1(-/- or CX(3CL1(-/- mice showed significantly decreased specific IgG production compared to wild type mice. CONCLUSION/SIGNIFICANCE: We propose a model whereby human follicular dendritic cells and T follicular helper cells release in the light zone of germinal centre soluble CX(3CL1 that attracts centrocytes. The functional implications of these results warrant further investigation.

  4. Molecular Mechanism of B Lymphocyte Activation and the Associated Diseases%B淋巴细胞活化分子事件及相关病理机制

    Institute of Scientific and Technical Information of China (English)

    徐银胜; 易骏阳; 高一仁; 刘册; 徐利玲; 刘万里

    2014-01-01

    B cells are important immune cells for humoral immune responses.B cell activation is a critical step for antibody production in response to pathogen invasion.In this review,we focused on the recent achievements in B cell studies using high-resolution high-speed live cell imaging techniques.These studies substantially improve our understanding of the molecular events governing the initiation of B cell activation.We summarized the recent studies about tonic B cell receptor (BCR) signaling which is thought to be responsible for B cell survival.We proposed several models to explain the origin of tonic BCR signaling.Meanwhile,we described the BCR signaling pathway driven by antigen stimulation,and discussed the possible mechanisms initiating B cell activation.Especially,we described how the high-resolution high-speed live cell imaging techniques help scientists to capture the dynamic events during B cell activation.Moreover,we discussed the molecular nature of the memory B cell with special focus placed on the roles of the evolutionarily conserved IgG cytoplasmic tail in memory antibody responses.Abnormal regulation of BCR activation may lead to diseases.In this regard,we discussed the recent findings in the last part of this review and also summarized the relationship of the mutation in the BCR inhibitory co-receptor FcγRⅡB and autoimmune diseases.Furthermore,we discussed the relationship between the mutation in BCR signaling molecules and B cell tumor.This work improves our understanding about B cell diseases and may benefit the clinical therapy.%B细胞是体液免疫的重要执行细胞,其活化是机体产生保护性抗体的关键步骤.目前人们对B细胞早期活化的动态分子事件和信号起始机制等仍然未知.本文将重点总结超高清成像技术和高速高分辨率活体成像技术在B细胞领域的应用,这些研究将帮助人们理解B细胞早期活化的机制.本文系列总结了静息态下维持B细胞存活的B细胞受体(Bcell receptor,BCR)滋养信号的研究进展,并提出了滋养信号来源的几种可能的模型.描述了抗原刺激导致的BCR活化的信号通路,并重点探讨了成像技术进步带来的关于BCR信号通路起始的机制探索这一免疫学领域的重大问题.结合高速高分辨率活细胞成像技术在免疫学领域的应用,抗原刺激后BCR活化过程中一系列动态变化过程和高级结构的形成能够被实时捕获.此外,还探讨了B细胞记忆性免疫发生的机制,重点阐述了亲和力成熟和BCR亚型转换,尤其是IgG(Immunoglobulin G)型BCR胞内尾巴对快速强烈的记忆性免疫反应的帮助.B细胞活化机制的调节过程发生异常会破坏正常的B细胞稳态平衡和免疫疾病的发生,本文总结抑制性调节受体FcγRⅡB(Fcγreceptor ⅡB)突变与自身免疫病的关系,以及BCR信号通路信号分子突变与B细胞肿瘤的关系,这些研究将加深人们对B细胞免疫疾病的认识和相应医疗手段的改进.

  5. Junctional adhesion molecule C (JAM-C) distinguishes CD27+ germinal center B lymphocytes from non-germinal center cells and constitutes a new diagnostic tool for B-cell malignancies.

    Science.gov (United States)

    Ody, C; Jungblut-Ruault, S; Cossali, D; Barnet, M; Aurrand-Lions, M; Imhof, B A; Matthes, T

    2007-06-01

    Differentiation of naïve B cells into plasma cells or memory cells occurs in the germinal centers (GCs) of lymph follicles or alternatively via a GC- and T-cell-independent pathway. It is currently assumed that B-cell lymphomas correlate to normal B-cell differentiation stages, but the precise correlation of several B-cell lymphomas to these two pathways remains controversial. In the present report, we describe the junctional adhesion molecule C (JAM-C), currently identified at the cell-cell border of endothelial cells, as a new B-cell marker with a tightly regulated expression during B-cell differentiation. Expression of JAM-C in tonsils allows distinction between two CD27+ B-cell subpopulations: JAM-C- GC B cells and JAM-C+ non-germinal B cells. The expression of JAM-C in different B-cell lymphomas reveals a disease-specific pattern and allows a clear distinction between JAM-C- lymphoproliferative syndromes (chronic lymphocytic leukemia, mantle cell lymphoma and follicular lymphoma) and JAM-C+ ones (hairy cell leukemia, marginal zone B-cell lymphoma). Therefore, we propose JAM-C as a new identification tool in B-cell lymphoma diagnosis.

  6. 运用BIOMED-2 PCR检测脑脊液中的恶性B淋巴细胞%Detection of Malignant B Lymphocytes in Cerebrospinal Fluid by using BIOMED-2 PCR

    Institute of Scientific and Technical Information of China (English)

    刘丽晓; 赵辉; 张为伟; 岳冬梅; 周晋

    2013-01-01

    本研究旨在建立一种检测弥漫性大B细胞淋巴瘤(DLB CL)中枢神经系统(CNS)累及患者脑脊液(CSF)中恶性B淋巴细胞的敏感的方法.对9例考虑有CNS累及风险的DLBCL患者采集其CSF,离心获取细胞沉淀,在直接裂解后运用BIOMED-2 PCR检测免疫球蛋白重链(IgH)基因重排(恶性B淋巴细胞特征性改变),并将此方法的敏感性与细胞学检测及流式细胞术进行比较.此外,通过一系列数量/浓度的肿瘤细胞,分析两种样品处理方式(细胞直接裂解法和传统DNA提取法)导致的敏感度差异,并评估直接裂解法联合BIOMED-2 PCR方案的敏感度.结果显示,BIOMED-2 PCR检测到5例DLBCL患者的CSF中存在克隆性IgH基因重排(恶性B淋巴细胞“阳性”),而细胞学检测和流式细胞术均只能明确检测2例为“阳性”,表明BIOMED-2 PCR敏感性高于细胞学检测和流式细胞术.另外,经过改进的样品处理方式——细胞直接裂解法比传统的DNA提取能获得更高的BIOMED-2PCR敏感度,前者可以检测到浓度低至1%、细胞数低至20个的肿瘤细胞.结论:细胞直接裂解联合BIOMED-2PCR是一种敏感的、非常适用于CSF(细胞数少)的检测方法,可辅助诊断DLBCL病例的CNS累及.

  7. Analysis of the antigen- and mitogen-induced differentiation of B lymphocytes from asymptomatic human immunodeficiency virus-seropositive male homosexuals. Discrepancy between T cell-dependent and T cell-independent activation.

    NARCIS (Netherlands)

    V.J.P. Teeuwsen; T. Logtenberg (Ton); C.H.J. Siebelink (Kees); J. Goudsmit (Jaap); F.G.C.M. Uytdehaag (Fons); A.D.M.E. Osterhaus (Ab); J.M.A. Lange (Joep)

    1987-01-01

    textabstractFive asymptomatic human immunodeficiency virus (HIV)-seropositive ; male homosexuals were immunized with the recall antigens tetanus toxoid (TT) and the three types of poliovirus present in diphtheria, tetanus, and polio vaccine. Four weeks after immunization, the in vivo response to boo

  8. EB病毒侵入宿主细胞机制的研究进展%The Entry of Epstein-Barr Virus into B Lymphocytes and Epithelial Cells During Infection

    Institute of Scientific and Technical Information of China (English)

    左埒莲; 朱美娟; 都树娟; 卢建红; 李桂源

    2014-01-01

    EB病毒(Epstein-barr virus,EBV),与多种人类疾病尤其是恶性肿瘤相关,包括单核细胞增多症、伯基特淋巴瘤和鼻咽癌等,其进入宿主细胞的机制仍是研究的热点.经过多年的研究,已经确定了EBV侵入宿主细胞时的部分关键蛋白以及不同的模式.病毒包膜糖蛋白gp350/220 (EBV glycoprotein 350/220)与B淋巴细胞表面受体CR2(Complement Receptor type 2)的相互作用以及其他病毒糖蛋白如gp42(EBV glycoprotein 42)、gB(EBV glycoprotein B)、gH(EBV glycoprotein H)和gL(EBV glycoprotein L)的相互作用,使得EBV能够有效侵入B淋巴细胞.由于绝大多数上皮细胞缺少CR2受体,病毒侵入上皮细胞的机制要比侵入B淋巴细胞复杂得多.主要有三种EBV进入上皮细胞的模式:①EBV通过感染的B淋巴细胞或郎罕氏细胞直接接触上皮细胞,“转移感染”进入上皮细胞;②EBV利用自身的相关蛋白与宿主相应的受体蛋白相结合后,通过膜的融合或内吞作用,感染上皮细胞;③感染EBV的上皮细胞经基底膜将病毒颗粒传递给邻近的细胞.本篇综述将介绍近年来在EBV进入B淋巴细胞与上皮细胞的相关机制的研究进展.

  9. 泌乳素对人B淋巴细胞HLA-DR表达的影响%Effects of prolactin on the expression of HLA-DR of human B lymphocyte

    Institute of Scientific and Technical Information of China (English)

    王洪兴; 李娜; 石瑛

    2005-01-01

    目的探讨泌乳素(PRL)与B淋巴细胞功能的关系.方法以生理浓度(10ng·ml-1)的人PRL刺激培养IM-9细胞系,并设置未刺激组、脂多糖(LPS)刺激组、PRL刺激组、LPS+PRL刺激组、LPS+溴隐停(Brc)刺激组和LPS+PRL+Brc刺激组;采用免疫细胞化学S-P染色法检测不同刺激组B淋巴细胞HLA-DR的表达情况.结果LPS刺激组和PRL刺激组HLA-DR的平均光密度(MOD)与未刺激组相比有明显增加(P<0.05);LPS+PRL刺激组HLA-DR的MOD与LPS、PRL刺激组相比明显增加(P<0.01);LPS+Brc刺激组HLA-DR的MOD与LPS刺激组与LPS+PRL+Brc刺激组相比均明显降低(P<0.05).结论PRL对B淋巴细胞有活化作用.

  10. 帕金森病患者外周血淋巴细胞亚群的变化规律%Clinical analysis of subpopulation of peripheral T and B lymphocytes in Chinese Parkinson′s disease patients

    Institute of Scientific and Technical Information of China (English)

    张思韵; 陈朝俊; 易黎; 徐评议; 孙丛丛; 张丽敏; 岑娈; 莫明树; 刘焯霖; 黄卫; 朱飞奇; 康平

    2014-01-01

    目的:探讨帕金森病( PD)患者外周血T、B淋巴细胞亚群指标的变化规律,评估其作为PD诊断及病情评估的生物学标记的价值。方法以2013年3月至2014年6月从中山大学附属第一医院神经科门诊/住院77例PD患者及体检中心82名健康老年人为研究对象。流式细胞术检测研究对象外周血中CD3+、CD3+CD4+、CD3+CD8+、CD19+淋巴细胞亚群百分比, t检验比较两组差异,多元线性回归分析PD组淋巴细胞亚群与其病程、病情严重程度及其药物剂量的相关性。结果PD患者外周血CD3+、CD3+CD4+T淋巴细胞百分比较对照组明显降低[(62±12)%比(66±9)%, P=0.04;(35±9)%比(38±7)%,P=0.02],尤其男性患者[(66±9)%比(61±13)%,P=0.02;(38±10)%比(33±9)%,P=0.01]。男性患者外周血CD3+T淋巴细胞百分比与其病程呈正相关( r=0.329,P=0.013,回归系数为1.423)。女性患者外周血CD3+CD8+T淋巴细胞百分比则与其病程呈负相关、与非运动症状评分呈正相关(r=-0.309,P=0.045;r=0.370,P=0.020;回归系数分别为-0.354,0.486)。结论 PD患者外周血的T淋巴细胞亚群比例失调,且存在性别差异。外周血淋巴细胞比例的变化可能有助于PD诊断及其病情进展的评估。%Objective To explore the variations of subpopulation of peripheral lymphocytes in Parkinson′s disease ( PD ) and locate its potential biomarkers for clinical evaluations.Methods The methods of direct immunostaining and flow cytometry were employed to test the percentages of CD3 +, CD3 +CD4 +, CD3 +CD8 +, CD19 +lymphocytes in blood samples of 77 PD patients and 82 healthy controls.And the percentages of CD3 +CD4 + and CD3 +CD8 + lymphocytes and the parameters of patients and health controls were analyzed.Results Compared to controls, the percentages of CD3 +, CD3 +CD4 +lymphocytes significantly decreased in PD patients ( (62 ±12)%vs (66 ±9)%, P=0.04;(35 ±9)%vs (38 ±7)%, P=0.02), especially in males ((66 ±9)%vs (61 ±13)%, P=0.02;(38 ±10)%vs (33 ±9)%, P=0.01)).Furthermore, the percentage of CD3 +lymphocytes had a positive correlation with the course of PD in male patients ( r =0.329, P =0.013, β=1.423 ) .And a negative correlation existed between the percentage of CD3 +CD4 +lymphocytes and the course of PD and there was a positive correlation with NMSS scale in female PD patients (r=-0.309, P=0.045, β=-0.354; r=0.370, P=0.020, β=0.486). Conclusion The variants in subpopulation of peripheral lymphocytes in PD patients may serve as a potential biomarker for diagnosing PD and predicting its clinical course.

  11. BSAP/Pax-5在B淋巴细胞发育、增殖、分化中的作用%Effect of BSAP/Pax-5 on the Development, Proliferation and Differentiation of B Lymphocyte Cell

    Institute of Scientific and Technical Information of China (English)

    谭余庆; 张永祥

    2001-01-01

    BSAP, a B cell lineage-specific activator protein, is a nucleus transcription factor and is en coded by the Pax-5 gene. It is a critical modulator of B cell development, proliferation and differentia tion. BSAP also influences B cell immunoglobulin secretion at later stages of B cell differentiation.%BSAp,一个B细胞特异性激活蛋白,由Pax-5转录的核蛋白。作为核转录因子,其在B细胞的发育、增殖和分化中起重要作用。同时也影响B细胞分化晚期的Ig的分泌。

  12. 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.

  13. Experiment list: SRX102972 [Chip-atlas[Archive

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

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    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 pedigree

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    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

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

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

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    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

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

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    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

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

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    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

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    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 Proj

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

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    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

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    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

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

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    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

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    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

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

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    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

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

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

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    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

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    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

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

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    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

  20. 流式细胞术检测B淋巴细胞表面免疫球蛋白轻链及临床意义%Surface immunoglobulin light-chain expression on B lymphocytes in neoplastic B-cell disorders and in non-neoplastic B-cell disorders

    Institute of Scientific and Technical Information of China (English)

    叶树俊; 张葵; 陈军浩; 顾光煜

    2007-01-01

    目的 探讨流式细胞术检测外周血B淋巴细胞表面免疫球蛋白(Ig)轻链的实验方法和临床意义.方法 采用流式细胞术,以CD19设门,分析了20例健康对照者和13例淋巴瘤患者B细胞表面Ig kappa与lambda型轻链的表达.结果 对照组kappa型轻链阳性B细胞为(51.4±5.2)%,lambda型轻链阳性B细胞为(39.2±4.3)%,两型轻链B细胞之比值为1.31±0.28;淋巴瘤患者B细胞中kappa型轻链8例(61.5%),lambda型轻链5例(38.5%),两型轻链B细胞的比值或者均小于0.01,或者大于56.78,显著超出健康人比值范围.结论 流式细胞术直接检测B细胞表面kappa轻链与lambda轻链的表达有助于鉴别反应性B淋巴细胞增生和肿瘤性慢性B淋巴细胞增生.

  1. Decreased effect of Rituximab on inhibition of granulocyte-macrophage colony forming unit of normal bone marrow and SLE patients by SLE's B-lymphocyte%Rituximab减少SLE患者B淋巴细胞对骨髓粒-巨噬细胞集落的抑制作用

    Institute of Scientific and Technical Information of China (English)

    李娟; 陆春; 罗绍凯

    2002-01-01

    目的:了解不同浓度Rituximab对SLE患者B淋巴细胞、对正常人及SLE患者骨髓粒-巨噬细胞集落形成单位(GM-CFU)抑制作用的影响及其机制.方法:体外用终浓度为0.1、0.5、1、3、6、9 μg/ml的Rituximab与SLE患者B淋巴细胞共同加入SLE患者及正常人骨髓GM-CFU的培养体系中,观察它们对SLE患者及正常人骨髓GM-CFU形成的影响,用流式细胞仪检测经不同浓度Rituximab处理前后SLE患者B淋巴细胞上的CD20表达水平,逆转录PCR法检测与终浓度为9 μg/ml Rituximab共同孵育前后SLE患者B淋巴细胞的IL-10 mRNA与β-actin的比值.结果:加入终浓度为0.1、0.5、1、3、6、9 μg/ml的Rituximab和SLE患者B淋巴细胞后,正常人骨髓GM-CFU产率分别为180±37、200±54、226±45、248±71、251±56、258±66个/105细胞,与不加Rituximab和SLE患者B淋巴细胞的正常人骨髓GM-CFU产率(256±80个/105细胞)比较,前二组P<0.05,后四组P>0.05,与仅加入SLE患者B淋巴细胞的正常人骨髓GM-CFU产率(199±92个/105细胞)对比,前二组P>0.05,后四组P<0.05.加入以上6种相同浓度的Rituximab和SLE患者B淋巴细胞后,SLE患者骨髓GM-CFU产率分别为119±71、116±78、177±68、202±49、217±52、227±48个/105细胞,与不加Rituximab和SLE患者B淋巴细胞的SLE患者骨髓GM-CFU产率(182±50个/105细胞)对比,前二组P<0.05,后四组P>0.05,与仅加入SLE患者B淋巴细胞的SLE患者骨髓GM-CFU产率(131±86个/105细胞)对比,前二组P>0.05,后四组P<0.05.Rituximab处理前SLE患者B淋巴细胞CD20+表达水平为(92±21)%,经用以上6种浓度的Rituximab处理后SLE患者B淋巴细胞CD20+表达水平分别为(83±53)%、(81±0)%、(75±34)%、(62±16)%、(38±22)%、(15±10)%,与Rituximab处理前的比较,前二组P>0.05,后四组P<0.05.与终浓度为9 μg/ml的Rituximab共同孵育前SLE患者B淋巴细胞IL-10mRNA与β-actin比值为4.6±2.8,共同育3 h后SLE患者B淋巴细胞IL-10mRNA与β-actin比值为2.4±1.3,两者差别有显著性,P<0.05.结论:Rituximab浓度在1 μg/ml以上时,可以减少SLE患者B淋巴细胞对SLE患者和正常人骨髓GM-CFU形成的抑制作用,Rituximab浓度越高,这种作用越明显,其机制与Rituximab减少SLE患者B淋巴细胞CD20、IL-10mRNA表达有关.

  2. 实验感染肝片吸虫山羊血液T、B淋巴细胞比例及激素水平变化%Changes of T- and B-lymphocytes Ratios and Hormone Levels in Goats Infested with F. hepatica

    Institute of Scientific and Technical Information of China (English)

    陈龙; 王丙云; 等

    2001-01-01

    为了深入了解动物感染肝片吸虫后免疫细胞和内分泌活动的变化,将6只健康山羊均分为感染I、Ⅱ组及对照组.I、Ⅱ组分别一次性口服感染肝片吸虫囊蚴200、500个/只,试验期17周,每周定时采血,测定血浆T、B淋巴细胞比例、皮质醇、胰岛素、甲状腺激素(T3、T4)等.结果表明,I、Ⅱ组山羊T淋巴细胞(%)分别从感染后4、6周开始低于或显著低于对照组,直至17周;而B淋巴细胞(%)变化与之相反.I、Ⅱ组山羊血浆皮质醇变化较大,总体水平高于对照组;T3、T4水平从第4周开始逐渐低于对照组,且在极低的水平上变动;I、Ⅱ组胰岛素水平与对照组相近.提示山羊急性感染肝片吸虫后,内分泌活动紊乱,体内细胞免疫反应抑制,而体液免疫反应增加,表现出山羊对肝片吸虫感染的耐受力和抵抗力较弱的特点.

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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...L818 || labexpid=SL818 || cell organism=human || cell description=B-Lymphocyte, Lymphoblastoid, Internatio...nal HapMap Project, CEPH/Utah pedigree 1463, Treatment: Epstein-Barr Virus transfor

  9. 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...SL1783 || labexpid=SL1783 || cell organism=human || cell description=B-Lymphocyte, Lymphoblastoid, Interna...tional HapMap Project, CEPH/Utah pedigree 1463, Treatment: Epstein-Barr Virus trans

  10. 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...L1782 || labexpid=SL1782 || cell organism=human || cell description=B-Lymphocyte, Lymphoblastoid, Internat...ional HapMap Project, CEPH/Utah pedigree 1463, Treatment: Epstein-Barr Virus transf

  11. B-CELLS SPECIFIC FOR BROMELAIN-TREATED ERYTHROCYTES ORE NOT DERIVED FROM ADULT-RAT BONE-MARROW

    NARCIS (Netherlands)

    DEBOER, NK; MEEDENDORP, B; AMMERLAAN, WAM; DEBOER, T; NIEUWENHUIS, P; KROESE, FGM

    1994-01-01

    As part of an evolutionary layered hematopoietic system, the B lymphocyte compartment consists of different lineages of B lymphocytes, which evolve sequentially during ontogeny. In mice, there is ample evidence for the existence of at least two lineages, a layer of B-1 cells (Ly-1 B cells) and the e

  12. 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

  13. Immune System

    Science.gov (United States)

    ... and mature there to become B cells or leave for the thymus gland, where they mature to become T cells. B lymphocytes and T lymphocytes have separate jobs to do: B lymphocytes are like the body's military intelligence system, seeking out their targets and sending defenses to ...

  14. Human peripheral blood B-Cell compartments: A crossroad in B-cell traffic

    NARCIS (Netherlands)

    M. Perez-Andres; B. Paiva; W.G. Nieto (Wendy); A. Caraux; A. Schmitz; J. Almeida (Julia); R.F. Vogt; G.E. Marti; A.C. Rawstron; M.C. van Zelm (Menno); J.J.M. van Dongen (Jacques); H.E. Johnsen (Hans); B. Klein (Binie); A. Orfao (Alberto)

    2010-01-01

    textabstractA relatively high number of different subsets of B-cells are generated through the differentiation of early B-cell precursors into mature B-lymphocytes in the bone marrow (BM) and antigen-triggered maturation of germinal center B-cells into memory B-lymphocytes and plasmablasts in lympho

  15. Human Peripheral Blood B-Cell Compartments : A Crossroad in B-Cell Traffic

    NARCIS (Netherlands)

    Perez-Andres, M.; Paiva, B.; Nieto, W. G.; Caraux, A.; Schmitz, A.; Almeida, J.; Vogt, R. F.; Marti, G. E.; Rawstron, A. C.; Van Zelm, M. C.; Van Dongen, J. J. M.; Johnsen, H. E.; Klein, B.; Orfao, A.

    2010-01-01

    A relatively high number of different subsets of B-cells are generated through the differentiation of early B-cell precursors into mature B-lymphocytes in the bone marrow (BM) and antigen-triggered maturation of germinal center B-cells into memory B-lymphocytes and plasmablasts in lymphoid tissues.

  16. Effect of radiation on cell interactions with respect to the phenomenon of inactivation of nonsyngeneic stem cells. Quantitative parameters of the regulatory action of. beta. -lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    Dozmorov, I.M.; Petrov, R.V.; Lutsenko, G.V.; Nikolaeva, I.S.; Rudneva, T.B. (Institut Biofiziki, Moscow (USSR))

    Quantitative regularities have been revealed in the regulatory action of B-lymphocytes from mouse lymph nodes on killer activity of T-lymphocytes of low electrophoretic motility. It was shown that the radiation-inducted charges in the mode of action of B-lymphocytes may be attributed to a decrease in the number of active CPllS.

  17. Classical natural ovine scrapie prions are detected in practical volumes of blood by lamb and transgenic mouse bioassay

    Science.gov (United States)

    In vitro ligand-based immunoassay studies revealed abnormal isoforms of prion protein (PrP-Sc) are primarily associated with B lymphocytes of scrapie-infected sheep. Our recent study also demonstrated efficient transmission of scrapie to lambs following a transfusion of B lymphocytes isolated from 5...

  18. 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, CEPH/Utah pedigree

  19. Experiment list: SRX199892 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ription=B-lymphocyte, lymphoblastoid, International HapMap Project, CEPH/Utah pedigree 1459, treatment: Epst...M12864 || cell organism=human || cell description=B-lymphocyte, lymphoblastoid, International HapMap Project, CEPH/Utah pedigree

  20. 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...igree 1463, treatment: Epstein-Barr Virus transformed ||... || cell=GM12891 || cell organism=human || cell description=B-lymphocyte, lymphoblastoid, International HapMap Project, CEPH/Utah ped

  1. Experiment list: SRX199861 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ription=B-lymphocyte, lymphoblastoid, International HapMap Project, CEPH/Utah pedigree 1459, treatment: Epst...M12872 || cell organism=human || cell description=B-lymphocyte, lymphoblastoid, International HapMap Project, CEPH/Utah pedigree

  2. 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, CEPH/Utah pedigree

  3. Experiment list: SRX150532 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available erm|Description=B-lymphocyte, lymphoblastoid, International HapMap Project, CEPH/Utah pedigree 1463, treatme...igree 1463, treatment: Epstein-Barr Virus transformed ||... || cell=GM12891 || cell organism=human || cell description=B-lymphocyte, lymphoblastoid, International HapMap Project, CEPH/Utah ped

  4. 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...Detail.aspx?Ref=GM12874 || cell=GM12874 || cell organism=Human || cell description=B-Lymphocyte, Lymphoblastoid, International

  5. 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...Detail.aspx?Ref=GM12864 || cell=GM12864 || cell organism=Human || cell description=B-Lymphocyte, Lymphoblastoid, International

  6. 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...ernational HapMap Project - CEPH/Utah - European Caucasi...type description=Chromatin IP Sequencing || cell=GM12878 || cell organism=human || cell description=B-lymphocyte, lymphoblastoid, Int

  7. 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 HapM...ll organism=human || cell description=lymphoblastoid, International HapMap Projec

  8. 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 Hap...ell organism=human || cell description=lymphoblastoid, International HapMap Proje

  9. 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... || datatype=DnaseSeq || datatype description=DNaseI HS Sequencing || cell description=B-lymphocyte, lymphoblastoid, International...-value cutoff: 0.05,1% ENCODE array platform validation tests || replicate=1,3,2 || cell description=lymphoblastoid, International

  10. 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..._Detail.aspx?Ref=GM12875 || cell=GM12875 || cell organism=Human || cell description=B-Lymphocyte, Lymphoblastoid, International

  11. 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...Detail.aspx?Ref=GM12865 || cell=GM12865 || cell organism=Human || cell description=B-Lymphocyte, Lymphoblastoid, International

  12. 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...Detail.aspx?Ref=GM12873 || cell=GM12873 || cell organism=Human || cell description=B-Lymphocyte, Lymphoblastoid, International

  13. 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...Detail.aspx?Ref=GM12872 || cell=GM12872 || cell organism=Human || cell description=B-Lymphocyte, Lymphoblastoid, International

  14. Pharm GKB: Leukemia, B-Cell, Acute [PharmGKB

    Lifescience Database Archive (English)

    Full Text Available UTR Alleles, Functions, and Amino Acid Translations are all sourced from dbSNP 144 Overview Alternate Names: Synonym Acute... B-Cell Leukemia; Acute B-Cell Leukemias; Acute B-Lymphocytic Leukemia; Acute... B-Lymphocytic Leukemias; Acute lymphoblastic leukaemia, Burkitt's type; Acute lymphoblastic leuka...emia, mature B-cell type; Acute lymphoblastic leukemia, Burkitt's type; Acute lymphoblastic leukemia, mature... B-cell type; B Cell Leukemia, Acute; B Lymphocytic Leukemia, Acute; B-ALL; B-Cell Leukemia, Acute

  15. RADIOIMMUNOTOXICOLOGICAL EFFECT OF ENRICHED URANIUM ON CENTRAL AND PERIPHERAL IMMUNE CELLS AND THE PROTECTIVE ACTION OF IL—1 AND IL—2

    Institute of Scientific and Technical Information of China (English)

    朱寿彭; 赖冠华; 等

    1994-01-01

    Accumulation of enriched 235U-UO2F2 in the body had injurious effects on the immune function of central and peripheral immune cells.After an intravenous injection of 235U-UO2F2,the spontaneous 3H-TdR incorporation in thymocytes and bone marrow cells decreased.with the thymocytes damaged more markedly.The proliferation ability of spleen T and B lymphocytes were both inhibited,with B lymphocytes inhibited more severely.In spleen B lymphocytes the IL-1 production and IL-2 consumption were diminshed.The inhibition of spleen B lymphocyte proliferation by 235U-UO2F2 was partially restored by adding exogenous IL-1 or IL-2 to the cultured lymphocytes obtained from 235U injected mice.

  16. Experiment list: SRX208213 [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...SRX208213 mm9 Unclassified Unclassified Blood B-Lymphocytes MeSH Description=Lympho

  17. Experiment list: SRX217132 [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...SRX217132 mm9 Unclassified Unclassified Blood B-Lymphocytes MeSH Description=Lympho

  18. Experiment list: SRX199986 [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...SRX199986 mm9 Unclassified Unclassified Blood B-Lymphocytes MeSH Description=Lympho

  19. Experiment list: SRX155012 [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...SRX155012 mm9 Unclassified Unclassified Blood B-Lymphocytes MeSH Description=Lympho

  20. Experiment list: SRX208207 [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...SRX208207 mm9 Unclassified Unclassified Blood B-Lymphocytes MeSH Description=Lympho

  1. B and T cell screen

    Science.gov (United States)

    Direct immunofluorescence; E-rosetting; T and B lymphocyte assays; B and T lymphocyte assays ... identifiers are added to distinguish between T and B cells. The E-rosetting test identifies T cells ...

  2. Experiment list: SRX189988 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available tion=B-lymphocyte, lymphoblastoid, International HapMap Project, CEPH/Utah, treatment: Epstein-Barr Virus tr...cyte, lymphoblastoid, International HapMap Project, CEPH/Utah, treatment: Epstein

  3. Experiment list: SRX080357 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ription=B-lymphocyte, lymphoblastoid, International HapMap Project, CEPH/Utah pedigree 1459, treatment: Epst...ternational HapMap Project, CEPH/Utah pedigree 1459, Treatment: Epstein-Barr Virus transformed || cell karyo

  4. Experiment list: SRX080420 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ription=B-lymphocyte, lymphoblastoid, International HapMap Project, CEPH/Utah pedigree 1459, treatment: Epst...nternational HapMap Project, CEPH/Utah pedigree 1459, Treatment: Epstein-Barr Virus transformed || cell kary

  5. Experiment list: SRX080349 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ription=B-lymphocyte, lymphoblastoid, International HapMap Project, CEPH/Utah pedigree 1459, treatment: Epst...nternational HapMap Project, CEPH/Utah pedigree 1459, Treatment: Epstein-Barr Virus transformed || cell kary

  6. 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...nternational HapMap Project, CEPH/Utah pedigree 1459, Treatment: Epstein-Barr Virus transformed || cell kary

  7. 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...nternational HapMap Project, CEPH/Utah pedigree 1459, Treatment: Epstein-Barr Virus transformed || cell kary

  8. Experiment list: SRX080404 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ription=B-lymphocyte, lymphoblastoid, International HapMap Project, CEPH/Utah pedigree 1459, treatment: Epst...ternational HapMap Project, CEPH/Utah pedigree 1459, Treatment: Epstein-Barr Virus transformed || cell karyo

  9. Experiment list: SRX100532 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available mesoderm|Description=B-lymphocyte, lymphoblastoid, International HapMap Project, CEPH/Utah pedigree 1463, tr...onal HapMap Project, CEPH/Utah pedigree 1463, treatment: Epstein-Barr Virus transformed || antibody antibody

  10. Experiment list: SRX080427 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ription=B-lymphocyte, lymphoblastoid, International HapMap Project, CEPH/Utah pedigree 1459, treatment: Epst...ternational HapMap Project, CEPH/Utah pedigree 1459, Treatment: Epstein-Barr Virus transformed || cell karyo

  11. The role of complement receptors type 1 (CR1, CD35) and 2 (CR2, CD21) in promoting C3 fragment deposition and membrane attack complex formation on normal peripheral human B cells

    DEFF Research Database (Denmark)

    Nielsen, Claus Henrik; Pedersen, Morten Løbner; Marquart, Hanne Vibeke

    2002-01-01

    Normal human B lymphocytes are known to activate the alternative pathway (AP) of complement, leading to C3-fragment deposition and membrane attack complex (MAC) formation. The process is mediated via complement receptor type 2 (CR2, CD21), with complement receptor type 1 (CR1, CD35) playing...... a subsidiary role. In this study, we examine the relative contributions of CR1 and CR2 to the deposition of C3 fragments and MAC on B lymphocytes under circumstances where all complement pathways are operational. C3-fragment deposition and MAC formation were assessed on human peripheral B lymphocytes......) bearing CR1, however, markedly reduced both C3-fragment deposition and MAC formation. Our data suggest that C3-fragment deposition and MAC formation on B lymphocytes in vivo may involve both AP and classical pathway activation, with CR1 contributing significantly to the latter. On the other hand...

  12. Experiment list: SRX186622 [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

  13. 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 Pr

  14. 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,

  15. 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/

  16. 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,

  17. 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/

  18. 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

  19. Effects of Sleep Deprivation on Mice Bone Marrow and Spleen B Lymphopoiesis.

    Science.gov (United States)

    Lungato, Lisandro; Nogueira-Pedro, Amanda; Carvalho Dias, Carolina; Paredes-Gamero, Edgar Julian; Tufik, Sergio; D'Almeida, Vânia

    2016-06-01

    B lymphocytes are immune cells crucial for the maintenance and viability of the humoral response. Sleep is an essential event for the maintenance and integrity of all systems, including the immune system (IS). Thus, sleep deprivation (SD) causes problems in metabolism and homeostasis in many cell systems, including the IS. In this study, our goal was to determine changes in B lymphocytes from the bone marrow (BM) and spleen after SD. Three-month-old male Swiss mice were used. These mice were sleep deprived through the modified multiple platform method for different periods (24, 48, and 72 h), whereas another group was allowed to sleep for 24 h after 72 h of SD (rebound group) and a third group was allowed to sleep normally during the entire experiment. After this, the spleen and BM were collected, and cell analyses were performed. The numbers of B lymphocytes in the BM and spleen were reduced by SD. Additionally, reductions in the percentage of lymphocyte progenitors and their ability to form colonies were observed. Moreover, an increase in the death of B lymphocytes from the BM and spleen was associated with an increase in oxidative stress indicators, such as DCFH-DA, CAT, and mitochondrial SOD. Rebound was not able to reverse most of the alterations elicited by SD. The reduction in B lymphocytes and their progenitors by cell death, with a concomitant increase in oxidative stress, showed that SD promoted a failure in B lymphopoiesis.

  20. Effects of benzene inhalation on lymphocyte subpopulations and immune response in mice.

    Science.gov (United States)

    Aoyama, K

    1986-08-01

    To clarify the immunotoxicity of benzene, the effects of benzene inhalation on T and B lymphocytes and immune responses in mice were examined. BALB/c male mice were exposed to 50 or 200 ppm benzene vapor, 6 hr/day for 7 or 14 consecutive days. T and B lymphocytes, in blood and spleen, were detected by the cytotoxicity assay with anti-Thy-1.2 monoclonal antibody and the membrane immunofluorescence test with anti-immunoglobulin antibody, respectively. Humoral immune response to sheep red blood cells was determined by the hemolytic plaque-forming cell assay. Cell-mediated immune response was measured by contact sensitivity (CS) to picryl chloride. The activity of suppressor cells was evaluated in spleen by the suppressive effect on passive transfer of CS. The ratio and absolute number of T and B lymphocytes in blood and spleen were depressed after a 7-day exposure at 50 ppm benzene. The depression of B lymphocytes was dose dependent and more intense than that of T lymphocytes. The ability to form antibodies was suppressed by benzene at all exposure levels, but the CS response was resistant to benzene inhalation and rather enhanced at 200 ppm exposure for 14 days. The activity of suppressor cells could not be detected at this dose level. These data show that benzene inhalation effects on humoral and cell-mediated immune responses are a result of the selective toxicity of benzene to B lymphocytes and suppressor T cells.

  1. Molecular cloning of a new immunomodulatory protein from Anoectochilus formosanus which induces B cell IgM secretion through a T-independent mechanism.

    Directory of Open Access Journals (Sweden)

    Yen-Chou Kuan

    Full Text Available An immunomodulatory protein (IPAF was purified and cloned from Anoectochilus formosanus, an Orchidaceae herbal plant in Asia. The major targeting immune cells of IPAF and its modulating effects toward B lymphocytes were investigated. Rapid amplification of cDNA ends (RACE was conducted to clone the IPAF gene, and the obtained sequence was BLAST compared on the NCBI database. MACS-purified mouse T and B lymphocytes were stimulated with IPAF and the cell proliferation, activation, and Igs production were examined. IPAF comprised a 25 amino acids signal peptide and a 138 amino acids protein which was homologous to the lectins from Orchidaceae plant. IPAF selectively induced the cell proliferation in mouse splenic B lymphocytes but not T lymphocytes. The IPAF-induced B cells exhibited increased CD69 and MHC class II expression, and a dose- and time-dependent enhancement in IgM production. These results suggested potential benefits of IPAF to strengthen the humoral immunity.

  2. Transient myelodysplastic syndrome in X-linked agammaglobulinemia with a novel Btk mutation.

    Science.gov (United States)

    Narula, Gaurav; Currimbhoy, Zinet

    2008-12-01

    X-linked agammaglobulinemia (XLA) is a rare disorder in which recurrent infections occur due to low serum globulins and circulating B lymphocytes caused by a mutation in the Bruton tyrosine kinase (Btk) gene. While myelodysplastic syndrome (MDS) associated with low B lymphocyte counts has been described, clonal cytogenetic abnormalities in confirmed cases of XLA have never been reported. We describe a case of XLA with a novel Btk mutation who also had a persistent clonal population in the bone marrow with abnormal cytogenetics in multiple chromosomes that resolved 1(1/2) years after treatment with IVIG, mimicking a picture of transient MDS.

  3. kappa+lambda+ dual receptor B cells are present in the human peripheral repertoire

    OpenAIRE

    1995-01-01

    It is a common notion that mature B lymphocytes express either kappa or lambda light (L) chains, although the mechanism that leads to such isotypic exclusion is still debated. We have investigated the extent of L chain isotypic exclusion in normal human peripheral blood B lymphocytes. By three-color staining with anti-CD19, anti-kappa, and anti-lambda antibodies we could estimate that 0.2-0.5% of peripheral blood B cells from healthy adults express both kappa and lambda on the cell surface. T...

  4. IMMUNOMODULATION OF SYNTHESIZED POLYMERS CONTAINING PHOSPHORUS IN THE BACKBONE —EFFECT ON THE PROLIFERATION OF LYMPHOCYTES

    Institute of Scientific and Technical Information of China (English)

    ZhuoRenxi; WangJun; 等

    1997-01-01

    The immunomodulation of several Charged synthetic polymers containing phosphorus in the backbone was studied in vitro through examining their inhibition or promotion effect on the proliferatioin of both T and B lymphocytes,It is found that polymers based on long chain alkyl ester of tyrosine exhibit immunomodulative activity.Negatively charged polymers show stimulative activity on LPS-induced B lymphocytes proliferation.Positively charged polymers exhibit inhibitory activity on both Con A-induced T lymphocytes and LPS-induced B lymplhyocytes proliferation.

  5. 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....

  6. 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...

  7. 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 in...

  8. Antibodies Against Human BLyS and APRIL Attenuate EAE Development in Marmoset Monkeys

    NARCIS (Netherlands)

    S.A. Jagessar (Anwar); N. Heijmans (Nicole); J. Bauer; E. Blezer (Erwin); J.D. Laman (Jon); T.S. Migone (Thi-Sau); M.N. Devalaraja (Matt); B.A. 't Hart (Bert)

    2012-01-01

    textabstractB lymphocyte stimulator (BLyS, also indicated as BAFF (B-cell activating factor) and CD257), and A Proliferation Inducing Ligand (APRIL, CD256) are two members of the TNF superfamily with a central role in B cell survival. Antibodies against these factors have potential therapeutic relev

  9. Antibodies Against Human BLyS and APRIL Attenuate EAE Development in Marmoset Monkeys

    NARCIS (Netherlands)

    Jagessar, S. Anwar; Heijmans, Nicole; Bauer, Jan; Blezer, Erwin L. A.; Laman, Jon D.; Migone, Thi-Sau; Devalaraja, Matt N.; 't Hart, Bert A.

    2012-01-01

    B lymphocyte stimulator (BLyS, also indicated as BAFF (B-cell activating factor) and CD257), and A Proliferation Inducing Ligand (APRIL, CD256) are two members of the TNF superfamily with a central role in B cell survival. Antibodies against these factors have potential therapeutic relevance in auto

  10. Experiment list: SRX019963 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ription=B-lymphocyte, lymphoblastoid, International HapMap Project, CEPH/Utah, treatment: Epstein-Barr Virus transformed...h.aspx?PgId=165&q=GM06990 || cell line=GM06990 || cell type=Epstein-Barr Virus transformed lymphoblastoid ||

  11. Experiment list: SRX019964 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available erm|Description=B-lymphocyte, lymphoblastoid, International HapMap Project, CEPH/Utah, treatment: Epstein-Barr Virus transformed.../Search.aspx?PgId=165&q=GM06990 || cell line=GM06990 || cell type=Epstein-Barr Virus transformed lymphoblast

  12. Analysis of 6912 unselected somatic hypermutations in human VDJ rearrangements reveals lack of strand specificity and correlation between phase II substitution rates and distance to the nearest 3' activation-induced cytidine deaminase target

    DEFF Research Database (Denmark)

    Ohm-Laursen, Line; Barington, Torben

    2007-01-01

    -23*01) from blood B lymphocytes enriched for CD27-positive memory cells. Analyses of 6,912 unique, unselected substitutions showed that in vivo hot and cold spots for the SHM of C and G residues corresponded closely to the target preferences reported for AID in vitro. A detailed analysis of all possible four...

  13. 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%), p

  14. 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...

  15. Alteration of peripheral blood lymphocyte subsets in acute pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Miroslawa Pietruczuk; Milena I Dabrowska; Urszula Wereszczynska-Siemiatkowska; Andrzej Dabrowski

    2006-01-01

    AIM: To evaluate peripheral blood lymphocyte subsets in patients with acute pancreatitis (AP).METHODS: Twenty patients with mild AP (M-AP) and 15 with severe AP (S-AP) were included in our study. Peripheral blood lymphocytes were examined at d 1-3, 5,10 and 30 by means of flow cytometry.RESULTS: A significant depletion of circulating lymphocytes was found in AP. In the early AP, the magnitude of depletion was similar for T- and B- lymphocytes. In the late course of S-AP, B-lymphocytes were much more depleted than T-lymphocytes. At d 10, strong shift in the CD7+/CD19+ ratio implicating predominance of Tover B-lymphocytes in S-AP was found. Among T-lymphocytes, the significant depletion of the CD4+ population was observed in M-AP and S-AP, while CD8+ cells were in the normal range. Lymphocytes were found to strongly express activation markers: CD69, CD25, CD28,CD38 and CD122. Serum interleukin-2 (IL-2), IL-4, IL-5,IL-10, interferon-γ (IFN-γ) and tumor necrosis factor-α(TNF-α) levels were significantly increased in both forms of AP. The magnitude of elevation of cytokines known to be produced by Th2 was much higher than cytokines produced by Th1 cells.CONCLUSION: AP in humans is characterized by significant reduction of peripheral blood T- and B-lymphocytes.

  16. Angioimmunoblastic T-Cell Lymphoma

    Science.gov (United States)

    Angioimmunoblastic T-Cell Lymphoma Overview Lymphoma is the most common blood cancer. The two main forms of lymphoma are ... develop into lymphomas: B-lymphocytes (B-cells) and T-lymphocytes (T-cells). Cancerous lymphocytes can travel to ...

  17. Peripheral T-Cell Lymphoma

    Science.gov (United States)

    Getting the Facts Peripheral T-Cell Lymphoma Overview Lymphoma is the most common blood cancer. The two main forms of lymphoma are Hodgkin lymphoma and ... develop into lymphomas: B-lymphocytes (B-cells) and T-lymphocytes (T-cells). Peripheral T-cell lymphoma (PTCL) ...

  18. T-Cell Lymphoma

    Science.gov (United States)

    Getting the Facts T-Cell Lymphoma Overview Lymphoma is the most common blood cancer. The two main forms of lymphoma are Hodgkin lymphoma ... develop into lymphomas: B-lymphocytes (B-cells) and T-lymphocytes (T-cells). T-cell lymphomas account for ...

  19. 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 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.

  20. Some features of immune status of animals infected with bovine leukosis background unbalanced on feeding

    OpenAIRE

    TURKO I.; SEMANYUK V.; PELENYO R.; KULYABA O.; TURKO YA.; VERHOLYUK M.

    2012-01-01

    The features of protein metabolism and immunity in cows with leukemia by unbalanced feeding of animals. The peculiarities of the dynamics of total protein, protein fractions, immunoglobulins, Tand B-lymphocytes in cows under violation of the sugar-protein ratio of diet and infection with a virus leukemia.

  1. B cell receptor-induced growth arrest and apoptosis in WEHI-231 immature B lymphoma cells involve cyclic AMP and Epac proteins

    NARCIS (Netherlands)

    Grandoch, Maria; de Jesus, Maider Lopez; Weernink, Paschal A. Oude; Weber, Artur-Aron; Jakobs, Karl H.; Schmidt, Martina

    2009-01-01

    Signaling by the B cell antigen receptor (BCR) is essential for B lymphocyte homeostasis and immune function. In immature B cells, ligation of the BCR promotes growth arrest and apoptosis, and BCR-driven balancing between pro-apoptotic extracellular signal-regulated kinase 1 and 2 (ERK1/2) and antia

  2. [Acute cerebellitis in infectious mononucleosis. One case (author's transl)].

    Science.gov (United States)

    Dandelot, J B; Samson, M; Augustin, P; Mihout, B; Parain, D

    1979-02-10

    A nineteen year old man present an original clinical case of acute cerebellitis in infectious mononucleosis. Eighteen months after the acute phase of the illness, there persisted a large deficit in the circulating B lymphocytes. A short review of pertinent litterature is presented and current physiopathological hypothesis are discussed. Briefly, delayed immunity and personal predisposition appear to play important etiological roles.

  3. [Comparative study of immunocompetent cells of dental pulp of intact teeth, teeth with carious lesion and its complications combined with parodontitis].

    Science.gov (United States)

    Moskovskiĭ, A V

    2007-01-01

    Results of the comparative immunohistochemical study of dental pulp by means of monoclonal antibodies to CD3, CD20, capital ES, CD68 are described. Pulp from the patients with caries, acute and chronic pulpitis in combination with periodontitis on different stages was studied, the qualitative and quantitative feature of dental pulp immune cells--T- and B-lymphocytes and macrophages was determined.

  4. 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 patients...

  5. Experiment list: SRX031181 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available m|Description=B-lymphocyte, lymphoblastoid, International HapMap Project, Yoruba in Ibadan, Nigera, treatmen...arch.aspx?PgId=165&q=NA19239 || cell type=lymphoblastoid cell line || origin=Yoruba from Ibadan, Nigeria (YR

  6. Experiment list: SRX031185 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available m|Description=B-lymphocyte, lymphoblastoid, International HapMap Project, Yoruba in Ibadan, Nigera, treatmen...arch.aspx?PgId=165&q=NA19239 || cell type=lymphoblastoid cell line || origin=Yoruba from Ibadan, Nigeria (YR

  7. Experiment list: SRX031180 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available m|Description=B-lymphocyte, lymphoblastoid, International HapMap Project, Yoruba in Ibadan, Nigera, treatmen...rch.aspx?PgId=165&q=NA19239 || cell type=lymphoblastoid cell line || origin=Yoruba from Ibadan, Nigeria (YRI

  8. Experiment list: SRX031183 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available m|Description=B-lymphocyte, lymphoblastoid, International HapMap Project, Yoruba in Ibadan, Nigera, treatmen...arch.aspx?PgId=165&q=NA19239 || cell type=lymphoblastoid cell line || origin=Yoruba from Ibadan, Nigeria (YR

  9. Experiment list: SRX031179 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available m|Description=B-lymphocyte, lymphoblastoid, International HapMap Project, Yoruba in Ibadan, Nigera, treatmen...rch.aspx?PgId=165&q=NA19239 || cell type=lymphoblastoid cell line || origin=Yoruba from Ibadan, Nigeria (YRI

  10. Experiment list: SRX031184 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available m|Description=B-lymphocyte, lymphoblastoid, International HapMap Project, Yoruba in Ibadan, Nigera, treatmen...arch.aspx?PgId=165&q=NA19239 || cell type=lymphoblastoid cell line || origin=Yoruba from Ibadan, Nigeria (YR

  11. Experiment list: SRX031182 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available m|Description=B-lymphocyte, lymphoblastoid, International HapMap Project, Yoruba in Ibadan, Nigera, treatmen...arch.aspx?PgId=165&q=NA19239 || cell type=lymphoblastoid cell line || origin=Yoruba from Ibadan, Nigeria (YR

  12. Experiment list: SRX031186 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available m|Description=B-lymphocyte, lymphoblastoid, International HapMap Project, Yoruba in Ibadan, Nigera, treatmen...arch.aspx?PgId=165&q=NA19239 || cell type=lymphoblastoid cell line || origin=Yoruba from Ibadan, Nigeria (YR

  13. Cytoreductive conditioning for severe combined immunodeficiency--help or hindrance?

    Science.gov (United States)

    Laberko, Alexandra; Gennery, Andrew R

    2015-01-01

    Use of chemotherapy-based conditioning-facilitated engraftment in patients with severe combined immunodeficiency (SCID) is contentious. In T- and NK lymphocyte-negative, B-lymphocyte-positive (T-B+NK+) and T-B-NK+ SCID, the osteo-medullary space is occupied by recipient hematopoietic stem cells and mature B-lymphocytes. The thymic niche is empty in T-B+NK+ SCID but fully occupied by developmentally arrested T-lymphocyte precursors in T-B-NK+ SCID. The outcome of infusion of donor stem cells differs and is dependent on genetic defect and the lymphocyte developmental arrest stage. At best, donor hematopoietic stem cell osteo-medullary engraftment induces normal B-lymphocyte function and long-term thymopoiesis; at worst, peripheral expansion of donor T-lymphocytes from the stem cell source results in a restricted T-lymphocyte receptor repertoire with possible B-lymphocyte failure. Conditioning improves immunoreconstitution but causes short- and long-term toxicities, and increased mortality. Newborn screening for SCID will propel the search for safe, effective methods of achieving donor cell engraftment and full immunoreconstitution without toxic sequalae.

  14. 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 nu

  15. Correction of murine rag2 severe combined immunodeficiency by lentiviral gene therapy using a codon-optimized RAG2 therapeutic transgene

    NARCIS (Netherlands)

    N.P. van Til (Niek); H. de Boer (Helen); N. Mashamba (Nomusa); A. Wabik (Agnieszka); M.W. Huston (Marshall W.); T.P. Visser (Trudi); R.J. Fontana (Robert); P.L. Poliani (Pietro); B. Cassani (Barbara); F. Zhang (Fang); A.J. Thrasher (Adrian); A. Anna (Villa); G. Wagemaker (Gerard)

    2012-01-01

    textabstractRecombination activating gene 2 (RAG2) deficiency results in severe combined immunodeficiency (SCID) with complete lack of T and B lymphocytes. Initial gammaretroviral gene therapy trials for other types of SCID proved effective, but also revealed the necessity of safe vector design. We

  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. Unraveling Mill-Rearranged Pedriatic Acute Myeloid Leukemia

    NARCIS (Netherlands)

    B.V. Balgobind (Brian)

    2011-01-01

    textabstractBlood cells are derived from hematopoietic stem cells (HSC) that reside in the bone marrow. HSC’s are multipotent and have the capacity to diff erentiate into the cells of all blood lineages, i.e. erythrocytes, platelets, neutrophils, eosinophils, basophils, monocytes, T and B lymphocyte

  18. Experiment list: SRX170356 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available SRX170356 hg19 TFs and others SMARCA4 Blood B-Lymphocytes MeSH Description=Lymphoid cells concerned with hum...oral immunity. They are short-lived cells resembling bursa-derived lymphocytes of b

  19. Autoimmune Disease

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    2009154 Expression of cellular FLICE inhibitory proteins in peripheral blood B lymphocytes in patients with systemic lupus erythematosus.DONG Jing(董婧),et al.Dept Dermatol,Wuhan 1st Hospital,Wuhan 430030.Chin J Dermatol,2009;42(4):226-229.

  20. Detergents in the indoor environment - what is the evidence for an allergy promoting effect?

    DEFF Research Database (Denmark)

    Poulsen, Lars K.; Clausen, S K; Glue, C

    2000-01-01

    of the intricate cellular interactions taking place along the immunological pathways. These include formation of IL-4 and IL-5 producing T helper lymphocytes type 2 and the B-lymphocyte isotype switch, which leads to production of specific IgE. Candidates for experimental studies of such phenomena on the cellular...

  1. Regulation of IgE production in mice

    NARCIS (Netherlands)

    Benner, R.; Savelkoul, H.F.J.

    1991-01-01

    Helper T-lymphocytes tightly regulate the proliferation and antibody production of B-lymphocytes by a variety of molecules called lymphokines. Molecular biology has provided the tools to produce large amounts of these regulatory molecules in highly purified "recombinant" form. Furthermore, monoclona

  2. JAK3 maps to human chromosome 19p12 within a cluster of protooncogenes and transcription factors

    Energy Technology Data Exchange (ETDEWEB)

    Hoffman, S.M.G.; Gordon, L.A.; Mohrenweiser, H.W. [Lawrence Livermore National Lab., CA (United States); Lai, Koon Siew [Univ. of North Carolina, Chapel Hill, NC (United States)] [and others

    1997-07-01

    The gene for the most recently discoverd member of a family of cytoplasmic tyrosine kinases, JAK3, was mapped to human chromosome 19p12 using polymerase chain reaction. JAK3 plays a role in the interleukin (IL)-2 signaling pathway that regulates T and B lymphocyte development and proliferation. 20 refs., 1 fig.

  3. 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....

  4. Radioadaptive response in human B- and CD8{sup +} T-lymphocytes as measured by the acridine orange stained micronuclei technique

    Energy Technology Data Exchange (ETDEWEB)

    Kim, H.S.; Choi, J.M.; Yang, K.H.; Kim, C.S.; Lim, Y.K.; Kim, C.S. [Korea Hydro and Nuclear Power Corporation, Radiation Health Research Institute, Seoul (Korea); Woon, J.H. [National Veterinary Research and Quarantine Service, Anyang (Korea)

    2003-07-01

    To investigate (1) the radiosensitive of B- versus T- lymphocytes and (2) the possible application of their sensitivity for adaptive response after treating with an adapting plus a challenge dose. In the present experiments, micronucleus analysis was performed in B- and CD8{sup +} matured T-lymphocytes of eight healthy volunteers exposed to {gamma}-rays. The number of radio-induced micronuclei was significantly higher in B-lymphocytes compared to T-lymphocytes in the dose range from 10 to 100cGy. To investigate adaptive response, whole blood samples were irradiated in vitro with a pretreatment dose of 1cGy {sup 137}Cs {gamma}-irradiation. Six hours after their initiation, groups of cultures were subsequently exposed to a challenge dose of 100cGy {gamma}-irradiation. Following stimulation with PHA and PWM for T- and B-lymphocyte cultivation, lymphocytes were fixed at 72 hours and stained with acridine orange dye. B-lymphocytes exhibited a greater induction of adaptive response than those of CD8{sup +} matured T-lymphocytes, and when pretreated with 1cGy significantly fewer micronuclei induced by the challenge dose of 100cGy {gamma}-irradiation. The results suggest that the lower dose pretreatments are able to induce a significantly higher adaptive response in human B-lymphocytes, and this adaptive response may result from the DNA repair mechanism, which may lead to less residual damage. (author)

  5. Rapid, non-targeted discovery of biochemical transformation and biomarker candidates in oncovirus-infected cell lines using LAESI mass spectrometry.

    Science.gov (United States)

    Shrestha, Bindesh; Sripadi, Prabhakar; Walsh, Callee M; Razunguzwa, Trust T; Powell, Matthew J; Kehn-Hall, Kylene; Kashanchi, Fatah; Vertes, Akos

    2012-04-18

    Finding insights into how viruses hijack metabolic processes and biomarkers for viral diseases often require hypotheses about target compounds and/or labelling techniques. Here we present a method based on laser ablation electrospray ionization mass spectrometry to rapidly identify potential protein and metabolite biomarkers of oncovirus infection in B lymphocytes.

  6. Transcription factor achaete-scute homologue 2 initiates follicular T-helper-cell development

    NARCIS (Netherlands)

    Liu, Xindong; Chen, Xin; Zhong, Bo; Wang, Aibo; Wang, Xiaohu; Chu, Fuliang; Nurieva, Roza I; Yan, Xiaowei; Chen, Ping; van der Flier, Laurens G; Nakatsukasa, Hiroko; Neelapu, Sattva S; Chen, Wanjun; Clevers, Hans; Tian, Qiang; Qi, Hai; Wei, Lai; Dong, Chen

    2014-01-01

    In immune responses, activated T cells migrate to B-cell follicles and develop into follicular T-helper (TFH) cells, a recently identified subset of CD4(+) T cells specialized in providing help to B lymphocytes in the induction of germinal centres. Although Bcl6 has been shown to be essential in TFH

  7. 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 benef

  8. Control of memory B cell responses by extrinsic and intrinsic mechanisms.

    Science.gov (United States)

    Wienands, Jürgen; Engels, Niklas

    2016-10-01

    Following primary activation, B lymphocytes generate a long-lived memory compartment to harness the organism for future reinfections by the same pathogen species. Only recently the composition and signaling signature of the scarce memory B cell pool could be explored in more detail. This review highlights current concepts of how B cells preserve their antigen experience at the cellular and molecular level.

  9. Circulating human B and plasma cells. Age-associated changes in counts and detailed characterization of circulating normal CD138(-) and CD138(+) plasma cells

    NARCIS (Netherlands)

    Caraux, Anouk; Klein, Bernard; Paiva, Bruno; Bret, Caroline; Schmitz, Alexander; Fuhler, Gwenny M.; Bos, Nico A.; Johnsen, Hans E.; Orfao, Alberto; Perez-Andres, Martin

    2010-01-01

    Generation of B and plasma cells involves several organs with a necessary cell trafficking between them. A detailed phenotypic characterization of four circulating B-cell subsets (immature-, naive-, memory- B-lymphocytes and plasma cells) of 106 healthy adults was realized by multiparametric flow cy

  10. Circulating human B and plasma cells. Age-associated changes in counts and detailed characterization of circulating normal CD138- and CD138+ plasma cells.

    Science.gov (United States)

    Caraux, Anouk; Klein, Bernard; Paiva, Bruno; Bret, Caroline; Schmitz, Alexander; Fuhler, Gwenny M; Bos, Nico A; Johnsen, Hans E; Orfao, Alberto; Perez-Andres, Martin

    2010-06-01

    Generation of B and plasma cells involves several organs with a necessary cell trafficking between them. A detailed phenotypic characterization of four circulating B-cell subsets (immature-, naïve-, memory- B-lymphocytes and plasma cells) of 106 healthy adults was realized by multiparametric flow cytometry. We show that CD10, CD27 and CD38 is the minimal combination of subsetting markers allowing unequivocal identification of immature (CD10(+)CD27(-)CD38(+), 6+/-6 cells/microL), naïve (CD10(-)CD27(-)CD38(-), 125+/-90 cells/microL), memory B lymphocytes (CD10(-)CD27(+)CD38(-), 58+/-42 cells/microL), and plasma cells (CD10(-)CD27(++)CD38(++), 2.1+/-2.1 cells/microL) within circulating CD19(+) cells. From these four subsets, only memory B lymphocytes and plasma cells decreased with age, both in relative and absolute counts. Circulating plasma cells split into CD138(-) (57+/-12%) and CD138(+) (43+/-12%) cells, the latter displaying a more mature phenotypic profile: absence of surface immunoglobulin, lower CD45 positivity and higher amounts of cytoplasmic immunoglobulin, CD38 and CD27. Unlike B lymphocytes, both populations of plasma cells are KI-67(+) and show weak CXCR4 expression.

  11. Immunology of the gastrointestinal tract and liver

    Energy Technology Data Exchange (ETDEWEB)

    Heyworth, M.F.; Jones, A.L.

    1988-01-01

    This book contains 11 chapters. Some of the chapter titles are: T cells and Other Non-B Lymphocytes; Mucosal Mast Cells and IgE; Genetic Aspects of Gastrointestinal Immunology; Immunological Functions of the Liver; Lymphocyte Migration and Mucosal Immunity; and Immunoglobulin Circulation and Secretion.

  12. KINETICS OF B-CELL SUBPOPULATIONS IN PERIPHERAL LYMPHOID-TISSUES - EVIDENCE FOR THE PRESENCE OF PHENOTYPICALLY DISTINCT SHORT-LIVED AND LONG-LIVED B-CELL SUBSETS

    NARCIS (Netherlands)

    DEENEN, GJ; KROESE, FGM

    1993-01-01

    A small proportion of the sIg+ B lymphocytes in peripheral lymphoid organs [22% in spleen and 6% in lymph node (LN)] in rat carries the Thy-1 antigen. These Thy-1 + B cells represent newly formed bone marrow (BM) derived (or immature) B cells. In this study we investigated the kinetic behavior of Th

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

    DEFF Research Database (Denmark)

    Fassi, Daniel El; 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...

  14. 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...

  15. 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 Pr

  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=GM12878 || cell organism=Human || cell description=lymphoblastoid || cell karyotype=relatively normal || cell lineage=Internatio...nal HapMap Project - CEPH/Utah - European Caucasion; Epstein-Barr Virus || cell sex

  17. 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=GM12878 || cell organism=Human || cell description=lymphoblastoid || cell karyotype=relatively normal || cell lineage=Internati...onal HapMap Project - CEPH/Utah - European Caucasion; Epstein-Barr Virus || cell se

  18. 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...atype description=Chromatin IP Sequencing || cell=GM06990 || cell organism=human || cell description=B-lymph

  19. Rituximab plus fludarabine and cyclophosphamide prolongs progression-free survival compared with fludarabine and cyclophosphamide alone in previously treated chronic lymphocytic leukemia

    DEFF Research Database (Denmark)

    Robak, Tadeusz; Dmoszynska, Anna; Solal-Céligny, Philippe;

    2010-01-01

    Rituximab, a monoclonal antibody that targets the CD20 cell surface antigen, has clinical activity in patients with non-Hodgkin's lymphoma and other B-lymphocyte disorders when administered alone or in combination with chemotherapy. Promising results have previously been reported in nonrandomized...

  20. Molecular aspects of multiple myeloma

    NARCIS (Netherlands)

    M.H.C. Bakkus (Marleen)

    1990-01-01

    textabstractMultiple myeloma (MM) is a malignant proliferating disorder of the B lymphocyte lineage, characterized by an increasing proportion of plasma cells in the bone marrow, a high and progressively increasing concentration of a homogeneous immunoglobulin in the blood and the occurrence of oste

  1. Increased frequency of immunoglobulin (Ig)A-secreting cells following Toll-like receptor (TLR)-9 engagement in patients with Kawasaki disease.

    Science.gov (United States)

    Giordani, L; Quaranta, M G; Marchesi, A; Straface, E; Pietraforte, D; Villani, A; Malorni, W; Del Principe, D; Viora, M

    2011-03-01

    Kawasaki disease (KD) is an acute vasculitis affecting mainly infants and children. Human B cells express Toll-like receptor (TLR)-9, whose natural ligands are unmethylated cytosine-guanine dinucleotide (CpG) motifs characteristic of bacterial DNA. The aim of this study was to clarify the pathogenesis of KD analysing the activation status of peripheral blood mononuclear cells (PBMC), focusing on B lymphocyte activation and functions. Ten patients and 10 age-matched healthy donors were recruited from the Bambino Gesù Hospital of Rome, Italy and enrolled into this study. We determined phenotype profile and immunoglobulin (Ig) production of PBMC from KD patients and age-matched controls. We found that the frequency of CD19(+) B lymphocytes and CD19(+) /CD86(+) activated B lymphocytes from KD patients during the acute phase before therapy was increased significantly. Moreover, B lymphocytes of acute-phase KD patients were more prone to CpG oligodeoxynucleotide (ODN) activation compared with the age-matched controls, as assessed by a significant increase of the number of IgA-secreting cells (SC). In the same patients we found a marked increase of IgM, IgG, interleukin (IL)-6 and tumour necrosis factor (TNF)-α production compared with the control group. In addition, in two convalescent KD patients, conventional treatment with intravenous immunoglobulin (IVIG) restored the normal frequency of CD19(+) B cells, the number of IgA-, IgM- and IgG-SC and the production of IL-6 and TNF-α. Our findings indicate that the percentages of peripheral B lymphocytes of acute-phase KD patients are increased and are prone to bacterial activation in terms of increased numbers of IgA-SC and increased production of IL-6 and TNF-α inflammatory cytokines. Thus, our data support the hypothesis of an infectious triggering in KD.

  2. Impaired Cellular Immunity in the Murine Neural Crest Conditional Deletion of Endothelin Receptor-B Model of Hirschsprung's Disease.

    Directory of Open Access Journals (Sweden)

    Ankush Gosain

    Full Text Available Hirschsprung's disease (HSCR is characterized by aganglionosis from failure of neural crest cell (NCC migration to the distal hindgut. Up to 40% of HSCR patients suffer Hirschsprung's-associated enterocolitis (HAEC, with an incidence that is unchanged from the pre-operative to the post-operative state. Recent reports indicate that signaling pathways involved in NCC migration may also be involved in the development of secondary lymphoid organs. We hypothesize that gastrointestinal (GI mucosal immune defects occur in HSCR that may contribute to enterocolitis. EdnrB was deleted from the neural crest (EdnrBNCC-/- resulting in mutants with defective NCC migration, distal colonic aganglionosis and the development of enterocolitis. The mucosal immune apparatus of these mice was interrogated at post-natal day (P 21-24, prior to histological signs of enterocolitis. We found that EdnrBNCC-/- display lymphopenia of their Peyer's Patches, the major inductive site of GI mucosal immunity. EdnrBNCC-/- Peyer's Patches demonstrate decreased B-lymphocytes, specifically IgM+IgDhi (Mature B-lymphocytes, which are normally activated and produce IgA following antigen presentation. EdnrBNCC-/- animals demonstrate decreased small intestinal secretory IgA, but unchanged nasal and bronchial airway secretory IgA, indicating a gut-specific defect in IgA production or secretion. In the spleen, which is the primary source of IgA-producing Mature B-lymphocytes, EdnrBNCC-/- animals display decreased B-lymphocytes, but an increase in Mature B-lymphocytes. EdnrBNCC-/- spleens are also small and show altered architecture, with decreased red pulp and a paucity of B-lymphocytes in the germinal centers and marginal zone. Taken together, these findings suggest impaired GI mucosal immunity in EdnrBNCC-/- animals, with the spleen as a potential site of the defect. These findings build upon the growing body of literature that suggests that intestinal defects in HSCR are not restricted

  3. A double antibody radioimmunoassay for measurement of IgG, IgA and IgM synthesized by human lymphocytes in vitro.

    Directory of Open Access Journals (Sweden)

    Asano,Taro

    1981-11-01

    Full Text Available To investigate cellular interactions between human T and B lymphocytes in various diseases, we established a technique to prove terminal differentiation of B lymphocytes into immunoglobulin synthesizing and secreting cells. We also established a double antibody radioimmunoassay to measure the amount of IgG, IgA and IgM synthesized and secreted in culture supernatants. Purified immunoglobulins were obtained from sera of patients with myeloma or macroglobulinemia. The peripheral blood lymphocytes from 25 normal individuals had the geometric mean synthetic rates of 1886 ng for IgG, 1607 ng for IgA and 1173 ng for IgM per 1 X 10(6 cells when cultured for nine days in the presence of pokeweed mitogen. The method is simple and sensitive, and is thought to be useful for examining human lymphocyte function in vitro.

  4. Waldenstrom macroglobulinemia with CD5+ expression presented as cryoglobulinemic glomerulonephropathy: a case report.

    Science.gov (United States)

    Kim, You Lim; Gong, Soo Jung; Hwang, Young Hwan; Joo, Jong Eun; Cho, Young Uk; Lee, Jung Ae; Sung, Su Ah; Lee, So Young; Kim, Nae Yoo

    2011-06-01

    Waldenstrom macroglobulinemia (WM) is a B-cell lymphoproliferative disorder associated with bone marrow involvement of lymphoplasmacytic lymphoma (LPL) and an IgM monoclonal gammopathy. Generally B-lymphocytes in LPL do not express CD5 that is important for differential diagnosis of B-cell lymphoproliferative disorders. In WM, various renal diseases and type I cryoglobulinemia are well described separately, but cryoglobulinemic glomerulonephropathy is very rarely reported. A 61-yr-old woman complained of generalized edema, cyanosis of the extremities in cold weather, visual disturbance, and pancytopenia. Bone marrow and renal biopsy showed CD5+ expressing B-cells and cryoglobulinemic glomerulonephropathy. With the diagnosis of WM, she received cyclophosphamide, doxorubicin, vincristine and prednisolone chemotherapy and got complete remission. Here, we report a rare case of WM associated with unusual expression of CD5+ B-lymphocytes and cryoglobulinemic glomerulonephropathy, and emphasize the importance of the clinical features in differentiating CD5+ B-cell lymphoproliferative disorders.

  5. Cast nephropathy and light-chain deposition disease in Waldenström macroglobulinemia.

    Science.gov (United States)

    Gnemmi, Viviane; Leleu, Xavier; Provot, François; Moulonguet, Florence; Buob, David

    2012-09-01

    Waldenström macroglobulinemia is a rare low-grade hematologic malignancy due to clonal proliferation of B lymphocytes responsible for immunoglobulin M (IgM) monoclonal gammopathy secreted in serum. This disease is characterized by lymphoplasmacytic tumoral infiltration of bone marrow and various organs, especially the liver and spleen. Kidney involvement in Waldenström macroglobulinemia has been described previously with reports of various forms of glomerular injury: large intracapillary IgM pseudothrombi, cryoglobulinemia-associated membranoproliferative glomerulonephritis, or amyloidosis. Interstitial infiltration by tumoral B lymphocytes is another classic pattern. Conversely, tubular involvement in the form of myeloma-like casts or basement membrane deposition of monoclonal light chain (light-chain deposition disease) is unusual. We report the occurrence of cast nephropathy associated with light-chain deposition disease in 2 patients with Waldenström macroglobulinemia, which resulted in severe and prolonged kidney failure.

  6. 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

  7. 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.

  8. Quantitative analysis of the acute and long-term CD4(+) T-cell response to a persistent gammaherpesvirus

    DEFF Research Database (Denmark)

    Christensen, Jan Pravsgaard; Doherty, P C

    1999-01-01

    The murine gammaherpesvirus 68 (MHV-68) replicates in respiratory epithelial cells, where it establishes a persistent, latent infection limited predominantly to B lymphocytes. The virus-specific CD4(+) T-cell response in C57BL/6 mice challenged intranasally with MHV-68 is detected first in the me......The murine gammaherpesvirus 68 (MHV-68) replicates in respiratory epithelial cells, where it establishes a persistent, latent infection limited predominantly to B lymphocytes. The virus-specific CD4(+) T-cell response in C57BL/6 mice challenged intranasally with MHV-68 is detected first...... were initially CD62Llow, with >80% maintaining that phenotype for the next 14 months. The overall conclusion is that MHV-68-specific CD4(+) T cells remain activated (CD62Llow) and at a stable frequency in the face of persistent infection....

  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. 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....... 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)......., 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...

  11. A Role For Mitochondria In Antigen Processing And Presentation.

    Science.gov (United States)

    Bonifaz, Lc; Cervantes-Silva, Mp; Ontiveros-Dotor, E; López-Villegas, Eo; Sánchez-García, Fj

    2014-09-23

    Immune synapse formation is critical for T lymphocyte activation, and mitochondria have a role in this process, by localizing close to the immune synapse, regulating intracellular calcium concentration, and providing locally required ATP. The interaction between antigen presenting cells (APCs) and T lymphocytes is a two-way signaling process. However, the role of mitochondria in antigen presenting cells during this process remains unknown. For APCs to be able to activate T lymphocytes, they must first engage in an antigen-uptake, -processing, and -presentation process. Here we show that HEL-loaded B lymphocytes, as a type of APCs, undergo a small but significant mitochondrial depolarization by 1-2 h following antigen exposure thus suggesting an increase in their metabolic demands. Inhibition of ATP synthase (oligomycin) or mitochondrial Ca(2+) uniporter (MCU) (Ruthenium red) had no effect on antigen uptake. Therefore, antigen processing and antigen presentation were further analyzed. Oligomycin treatment reduced the amount of specific MHC-peptide complexes but not total MHC II on the cell membrane of B lymphocytes which correlated with a decrease in antigen presentation. However, oligomycin also reduced antigen presentation by B lymphocytes that endogenously express HEL and by B lymphocytes loaded with the HEL48-62 peptide, although to a lesser extent. ATP synthase inhibition and MCU inhibition had a clear inhibitory effect on antigen processing (DQ-OVA). Taking together these results suggest that ATP synthase and MCU are relevant for antigen processing and presentation. Finally, APCs mitochondria were found to re-organize towards the APC-T immune synapse. This article is protected by copyright. All rights reserved.

  12. Lymphoreticular cells in human brain tumours and in normal brain.

    OpenAIRE

    1982-01-01

    The present investigation, using various rosetting assays of cell suspensions prepared by mechanical disaggregation or collagenase digestion, demonstrated lymphoreticular cells in human normal brain (cerebral cortex and cerebellum) and in malignant brain tumours. The study revealed T and B lymphocytes and their subsets (bearing receptors for Fc(IgG) and C3) in 5/14 glioma suspensions, comprising less than 15% of the cell population. Between 20-60% of cells in tumour suspensions morphologicall...

  13. The discovery and development of belimumab: the anti-BLyS–lupus connection

    OpenAIRE

    Stohl, William; Hilbert, David M.

    2012-01-01

    For the first time in more than 50 years, the US Food and Drug Administration has approved a drug specifically for the treatment of systemic lupus erythematosus (SLE). This drug, belimumab (Benlysta), is a human monoclonal antibody that neutralizes the B-cell survival factor, B-lymphocyte stimulator (BLyS). The approval of belimumab combined a pioneering approach to genomics-based gene discovery, an astute appreciation of translational medicine, a disciplined clinical strategy, a willingness ...

  14. Antibodies Against Human BLyS and APRIL Attenuate EAE Development in Marmoset Monkeys

    OpenAIRE

    Jagessar, Anwar; Heijmans, Nicole; Bauer, J.; Blezer, Erwin; Laman, Jon; Migone, Thi-Sau; Devalaraja, Matt; Hart, Bert

    2012-01-01

    textabstractB lymphocyte stimulator (BLyS, also indicated as BAFF (B-cell activating factor) and CD257), and A Proliferation Inducing Ligand (APRIL, CD256) are two members of the TNF superfamily with a central role in B cell survival. Antibodies against these factors have potential therapeutic relevance in autoimmune inflammatory disorders with a proven pathogenic contribution of B cells, such as multiple sclerosis (MS). In the current study we performed a multi-parameter efficacy comparison ...

  15. Mechanisms That Regulate Epstein-Barr Virus EBNA-1 Gene Transcription during Restricted Latency Are Conserved among Lymphocryptoviruses of Old World Primates

    OpenAIRE

    1999-01-01

    Epstein-Barr virus (EBV), the only known human lymphocryptovirus (LCV), displays a remarkable degree of genetic and biologic identity to LCVs that infect Old World primates. Within their natural hosts, infection by these viruses recapitulates many key aspects of EBV infection, including the establishment of long-term latency within B lymphocytes, and is therefore a potentially valuable animal model of EBV infection. However, it is unclear whether these LCVs have adopted or maintained the same...

  16. 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

  17. Profile of obinutuzumab for the treatment of patients with previously untreated chronic lymphocytic leukemia

    OpenAIRE

    Hill BT; Kalaycio M

    2015-01-01

    Brian T Hill, Matt Kalaycio Department of Hematology and Medical Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA Abstract: Chronic lymphocytic leukemia (CLL) is a hematologic malignancy derived from a clonal population of mature B-lymphocytes characterized by relatively low CD20 antigen expression. Although the disease often takes an indolent course, the majority of patients will eventually require therapy. Standard treatment for medically fit patients includes puri...

  18. Lymphomas of large cells.

    Science.gov (United States)

    Staples, W G; Gétaz, E P

    1977-09-03

    Historial aspects of the classification of large-cell lymphomas are described. Immunological characterization of the lymphomas has been made possible by identification of T and B lymphocytes according to their cell membrane surface characteristics. The pathogenesis of lymphomas has been clarified by the germinal (follicular) centre cell concepts of Lennert and Lukes and Collins. The various classifications are presented and compared. Whether these subdivisions will have any relevance in the clinical context remains to be seen.

  19. Taking Advantage: High Affinity B cells in the Germinal Center Have Lower Death Rates, But Similar Rates of Division Compared to Low Affinity Cells1

    OpenAIRE

    2009-01-01

    B lymphocytes producing high affinity antibodies (Abs) are critical for protection from extracellular pathogens, such as bacteria and parasites. The process by which high affinity B cells are selected during the immune response has never been elucidated. Though it has been shown that high affinity cells directly outcompete low affinity cells in the germinal center (GC)2, whether there are also intrinsic differences between these cells has not been addressed. It could be that higher affinity c...

  20. Pre-existing T- and B-cell defects in one progressive multifocal leukoencephalopathy patient.

    Directory of Open Access Journals (Sweden)

    Alessandra Sottini

    Full Text Available Progressive multifocal leukoencephalopathy (PML usually occurs in patients with severe immunosuppression, hematological malignancies, chronic inflammatory conditions or receiving organ transplant. Recently, PML has also been observed in patients treated with monoclonal antibodies. By taking advantage of the availability of samples from a multiple sclerosis (MS patient treated with natalizumab, the antibody anti-α4 integrin, who developed PML and was monitored starting before therapy initiation, we investigated the fate of T and B lymphocytes in the onset of PML. Real-time PCR was used to measure new T- and B-cell production by means of T-cell receptor excision circle (TREC and K-deleting recombination excision circle (KREC analysis and to quantify transcripts for CD34, terminal-deoxynucleotidyltransferase, and V pre-B lymphocyte gene 1. T- and B-cell subsets and T-cell heterogeneity were measured by flow cytometry and spectratyping. The data were compared to those of untreated and natalizumab-treated MS patients and healthy donors. Before therapy, a patient who developed PML had a low TREC and KREC number; TRECs remained low, while KRECs and pre-B lymphocyte gene 1 transcripts peaked at 6 months of therapy and then decreased at PML diagnosis. Flow cytometry confirmed the deficient number of newly produced T lymphocytes, counterbalanced by an increase in TEMRA cells. The percentage of naive B cells increased by approximately 70% after 6 months of therapy, but B lymphocyte number remained low for the entire treatment period. T-cell heterogeneity and immunoglobulins were reduced. Although performed in a single patient, all results showed that an immune deficit, together with an increase in newly produced B cells a few months after therapy initiation, may predispose the patient to PML. These findings indicate the TREC/KREC assay is a potential tool to identify patients at risk of developing PML and may provide insights into the immunological

  1. [Studies on immunocompetent constituents of Patrinia scabra Bunge].

    Science.gov (United States)

    Gu, Zhengbing; Chen, Xinjian; Yang, Genjin; Li, Tingzhao; Liu, Wenyong; Zhang, Weidong

    2002-03-01

    Five compounds were isolated from the roots of Patrinia scabra Bunge separated and purified on sillica gel column chromatography. Their structures were elucidated on the physico-chemical properties and spectral data as lariciresinol(I), syringaresinol(II), scopoletin(III), quercetin(IV), ferulaic acid(V). All compounds were obtained from P. scabra for the first time. In vitro biological test of these compounds showed that syringaresinol was able to stimulate T and B lymphocyte proliferation.

  2. 转录因子Blimp-1在浆细胞发育中的作用%The Role Transcription Factor Blimp-1 in Plasma Cell Development

    Institute of Scientific and Technical Information of China (English)

    邓少丽; 程小星

    2006-01-01

    转录因子Blimp-1(B lymphocyte induced maturation protein 1)(人的蛋白被称为PRDI-BF1)是具有5个锌指结构的980000D蛋白,它可以诱导成熟B淋巴细胞发育为浆细胞并分泌抗体,因此被称为"B淋巴细胞终极分化的主调控子".

  3. Plasma cells negatively regulate the follicular helper T cell program

    OpenAIRE

    2010-01-01

    B lymphocytes differentiate into antibody-secreting cells under the antigen-specific control of follicular helper T (TFH) cells. Here, we demonstrate that isotype-switched plasma cells expressed MHCII, CD80 and CD86 and intracellular machinery required for antigen presentation. Antigen-specific plasma cells could access, process and present sufficient antigen in vivo to induce multiple TH cell functions. Importantly, antigen-primed plasma cells failed to induce interleukin 21 or Bcl-6 in naïv...

  4. [Genetic bases of diversity of the repertoire of immunoglobulins in application to diagnostics of clonality of B-cell lymphoid populations].

    Science.gov (United States)

    Zakharova, E S; Kazilo, N A; Stefanov, D N; Sinitsina, M N; Kovrigina, A M

    2011-06-01

    Molecular mechanisms underlying the formation of B-cell lymphomas in connection with processes associated with the maturation of B lymphocytes are reviewed. The currently used diagnostic methods do not always distinguish lymphomas from reactive changes of the lymphoid tissue. The principle of the molecular genetic method ofclonality detection in lymphocyte populations, technical problems, and the strategy of its application in clinical diagnostics of lymphomas are described in detail.

  5. Pathogenesis of Cell Injury by Rickettsia conorii.

    Science.gov (United States)

    1984-06-15

    Yalaysia; Rhipicephalus simus, Amblyomma varieqatum, A. cohaerens, and A. gemma in Ethiopia; and Rhipicephalus bursa, Hyallomma marqinatum, H. lusitanicum...collected prior to the start of this contract presents a study of infection of genetically immunodeficient mice with R. conorii. In order to determine...the definitive importance of T- and B-lymphocytes in immunity to Rickettsa conor’i, mice genetically deficient in T-cells, B-cells, or both T- and B

  6. Sleep Deprivation in Humans, Immunodepression and Glutamine Supplementation

    Science.gov (United States)

    2007-11-02

    centrifuged at 5-8˚C, and the supernatant removed and stored at -20˚C. The samples were measured using a quantitative sandwich enzyme immunoassay ...numbers and differentials; platelet counts; haemoglobin ( Hb ), haematocrit (Hct), mean corpuscular volume (MCV); CD19+ B-lymphocyte cell counts...of caffeine were measured using a homogeneous enzyme immunoassay technique and the COBAS Mira Plus Clinical Analyser. Antioxidant capacity: A

  7. MicroRNAs in Pediatric Acute Lymphoblastic Leukemia: Small players with huge potential

    OpenAIRE

    Schotte, Diana

    2011-01-01

    textabstractHematopoiesis is a dynamic balance of cellular proliferation, survival, apoptosis and differentiation in which the pluripotent hematopoietic stem cell gives rise to lymphoid and myeloid precursors of blood cells. The B-lymphoid precursor sequentially differentiates from proB-cells into common/preB-cells and fi nally yields mature B-lymphocytes. The T-lymphoid precursor generates thymocytes or proT-cells that further differentiate into T-lymphocytes. The myeloid precursor gives ris...

  8. 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.

  9. Lymphoepithelioma-Like Carcinoma of the Skin Treated with Wide Local Excision and Chemoradiation Therapy: A Case Report and Review of the Literature

    Science.gov (United States)

    2012-01-01

    oral cavity mucositis. He received concurrent cisplatin (20 milligram per meter squared) weekly for five weeks. He was also referred to an outside...of T and B lymphocytes [5, 8] (Figure 1). These cytologic features are similar to those of metastatic nasopharyngeal carcinoma but are largely...have any cytological atypia. Management should involve a complete head and neck exam to include evaluation of the nasopharynx to rule out metastasis

  10. Steroid-resistant autoimmune thrombocytopenia in systemic lupus erythematosus treated with rituximab

    Directory of Open Access Journals (Sweden)

    Vasudha V Sardesai

    2015-01-01

    Full Text Available Systemic Lupus Erythematosus (SLE is a multisystem disorder characterized by production of numerous autoantibodies, some of which have pathogenic consequences and result in considerable morbidity. Herein, we present a case of 48-year-old female with SLE having autoimmune hemolytic anemia, autoimmune thrombocytopenia, renal involvement, and recurrent flares of skin manifestations. She did not respond to the conventional therapy and was controlled and treated with Rituximab, a chimeric, monoclonal antiCD20 antibody, which specifically depletes B lymphocytes.

  11. Persistence of high CD40 and CD40L expression after restorative proctocolectomy for ulcerative colitis

    Institute of Scientific and Technical Information of China (English)

    Lino Polese; Mauro Frego; Davide F D'Amico; Tmerio Angriman; Giuseppe De Franchis; Attilio Cecchetto; Giacomo C. Sturniolo; Renata D'Incà; Marco Scarpa; Cesare Ruffolo; Lorenzo Norberto

    2005-01-01

    AIM: To focus on the role of CD40 and CD40L in their pathogenesis.METHODS: We analyzed by immunohistochemistry the CD40 and CD40L expression in the pouch mucosa of 28 patients who had undergone RPC for UC, in the terminal ileum of 6 patients with UC and 11 healthy subjects. We also examined by flow cytometry the expression of CD40 by B lymphocytes and monocytes in the peripheral blood of 20 pouch patients, 15 UC patients and 11 healthy controls.RESULTS: Ileal pouch mucosa leukocytes presented a significantly higher expression of CD40 and CD40L as compared to controls. This alteration correlated with pouchitis, but was also present in the healthy pouch and in the terminal ileum of UC patients. CD40 expression of peripheral B lymphocytes was significantly higher in patients with UC and pouch, respect to controls. Increased CD40 levels in blood B cells of pouch patients correlatedwith the presence of spondyloarthropathy, but not with pouchitis, or inflammatory indices.CONCLUSION: High CD40 expression in the ileal pouch mucosa could be implied in the pathogenesis of pouchitis following proctocolectomy for UC, whereas its increased levels on peripheral blood B lymphocytes are associated with the presence of extraintestinal manifestations.

  12. Comparative In Vitro Immune Stimulation Analysis of Primary Human B Cells and B Cell Lines

    Science.gov (United States)

    Van Belle, Kristien; Herman, Jean; Boon, Louis; Waer, Mark

    2016-01-01

    B cell specific immunomodulatory drugs still remain an unmet medical need. Utilisation of validated simplified in vitro models would allow readily obtaining new insights in the complexity of B cell regulation. For this purpose we investigated which human B lymphocyte stimulation assays may be ideally suited to investigate new B lymphocyte immunosuppressants. Primary polyclonal human B cells underwent in vitro stimulation and their proliferation, production of immunoglobulins (Igs) and of cytokines, and expression of cell surface molecules were analysed using various stimuli. ODN2006, a toll-like receptor 9 (TLR9) agonist, was the most potent general B cell stimulus. Subsequently, we investigated on which human B cell lines ODN2006 evoked the broadest immunostimulatory effects. The Namalwa cell line proved to be the most responsive upon TLR9 stimulation and hence may serve as a relevant, homogeneous, and stable B cell model in an in vitro phenotypic assay for the discovery of new targets and inhibitors of the B cell activation processes. As for the read-out for such screening assay, it is proposed that the expression of activation and costimulatory surface markers reliably reflects B lymphocyte activation. PMID:28116319

  13. Phenotypic modulation of chronic lymphocytic leukemia cells by phorbol ester: induction of IgM secretion and changes in the expression of B cell-associated surface antigens.

    Science.gov (United States)

    Gordon, J; Mellstedt, H; Aman, P; Biberfeld, P; Klein, G

    1984-01-01

    Freshly explanted neoplastic populations from 22 cases of phenotypically well-characterized chronic type B lymphocytic leukemia were studied for their capacity to respond to the phorbol ester TPA in vitro. In all but four cases the secretion of IgM was either induced or increased, often to a high level. In contrast, the export of free immunoglobulin (Ig) light chains, an almost consistent feature of the B lymphocytic leukemias, remained relatively constant after TPA treatment. Parallel changes in leukemic cell surface phenotype were probed with both "conventional" and monoclonal antibodies, revealing some modulation of markers in every case investigated. A diminution in the level of surface Ig (preferentially IgD) and the accumulation of cytoplasmic Ig observed after phorbol ester treatment were accompanied by a corresponding reduction or loss of the B1 antigen and usually of B2 when present. The most consistent change induced by TPA was the appearance of BB-1, a marker of activated B lymphocytes, which was rarely expressed on fresh leukemic cells. Another marker of activated lymphocytes, LB-1, was also often induced or increased in its expression after exposure of the cells to TPA. The magnitude of the TPA response appeared to relate to the stage of maturation arrest of the individual leukemic clones rather than to any clinical parameter explored. The significance of the findings to normal B cell differentiation and their potential clinical utility are discussed.

  14. Signalling via MHC class II molecules modifies the composition of GEMs in APC.

    Science.gov (United States)

    Setterblad, N; Becart, S; Charron, D; Mooney, N

    2001-01-01

    Major histocompatibility complex (MHC) class II molecules are responsible for peptide presentation to helper T lymphocytes and as such play an essential role in the immune response. These molecules transmit intracellular signals leading to diverse consequences in B lymphocytes including proliferation and apoptosis. Recent studies have revealed that glycolipid enriched membrane microdomains (GEMs) behave as signalling platforms for a variety of lymphocyte receptors. We have quantified human leucocyte antigen (HLA)-DR molecules localized in GEMs in human B lymphocytes. Use of a model imitating the interaction of HLA-DR with a T-cell receptor (TCR) modified the constituents of the HLA-DR-enriched GEMs. Confocal microscopy demonstrated a recruitment of HLA-DR and the ganglioside GM1 at the site of HLA-DR interaction with the stimulating ligand. Moreover, cholesterol depletion efficiently impaired this recruitment. Co-localizing proteins detected in HLA-DR-enriched GEMs include protein kinase C (PKC)-delta and actin. These data reveal that MHC class II antigens are localized in GEMs in mature human B lymphocytes and indicates that the formation of the immunological synapse regulates the composition of HLA-DR enriched GEMs in the antigen presenting cell (APC).

  15. TRPC3 amplifies B-cell receptor-induced ERK signalling via protein kinase D-dependent Rap1 activation.

    Science.gov (United States)

    Numaga-Tomita, Takuro; Nishida, Motohiro; Putney, James W; Mori, Yasuo

    2016-01-15

    Sustained activation of extracellular-signal-regulated kinase (ERK) has an important role in the decision regarding the cell fate of B-lymphocytes. Recently, we demonstrated that the diacylglycerol-activated non-selective cation channel canonical transient receptor potential 3 (TRPC3) is required for the sustained ERK activation induced by the B-cell receptor. However, the signalling mechanism underlying TRPC3-mediated ERK activation remains elusive. In the present study, we have shown that TRPC3 mediates Ca(2+) influx to sustain activation of protein kinase D (PKD) in a protein kinase C-dependent manner in DT40 B-lymphocytes. The later phase of ERK activation depends on the small G-protein Rap1, known as a downstream target of PKD, whereas the earlier phase of ERK activation depends on the Ras protein. It is of interest that sustained ERK phosphorylation is required for the full induction of the immediate early gene Egr-1 (early growth response 1). These results suggest that TRPC3 reorganizes the BCR signalling complex by switching the subtype of small G-proteins to sustain ERK activation in B-lymphocytes.

  16. Ontogeny of the fetal immune system: study on pregnancies with Rh-isoimmunization and nonimmune fetal hydrops.

    Science.gov (United States)

    Noia, G; Romano, D; De Santis, M; Gozzo, M L; Colacicco, L; Mariorenzi, S; Straface, G; Rumi, C; Caruso, A; Mancuso, S

    1999-01-01

    This study aims at observing and comparing the antigen expression of some fetal T- and B-lymphocyte subpopulations in Rh-isoimmunization, which determines anemic hypoxia in the fetus, and nonimmune fetal hydrops (NIFH) which, even if there are some etiological factors involved, causes hipoxic hypoxia in the fetus. Twelve fetuses were studied by way of 30 fetal blood samples obtained by ultrasound-guided cordocentesis between the 20th and 36th gestational week. Twenty-four blood samples in all where taken from the eight fetuses with Rh-isoimmunization. Six blood samples were obtained from the four fetuses with NIFH. The lymphocyte phenotypes studied by monoclonal antibodies and flow cytometry were the following: CD3, CD4, CD8, expression of T-lymphocyte subpopulations; BsIg, CD19, expression of B-lymphocyte subpopulations. We observed a near-normal maturation process in fetuses with Rh isoimmunization, whereas in fetuses with NIFH we observed inhibition and/or delayed expression of T-lymphocytes. An early and increased B-lymphocyte activation marked a cooperation between the two systems in the early gestational periods.

  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. Immunotoxicological effects of benzene inhalation in male Sprague-Dawley rats.

    Science.gov (United States)

    Robinson, S N; Shah, R; Wong, B A; Wong, V A; Farris, G M

    1997-05-16

    The inhalation of benzene is toxic to various components of the immunologic system in rodents. Spleen and thymus weights, total spleen and femur marrow cell counts, enumeration of spleen B- and T-lymphocytes, and an assessment of humoral immunocompetence, were used to evaluate the immunotoxicity of benzene in male Sprague-Dawley rats. Rats were exposed to 0, 30, 200 or 400 ppm benzene for 6 h/day, 5 days/week for 2 or 4 weeks. An early indicator of immunotoxicity was a reduction in the number of B-lymphocytes after 2 weeks of 400 ppm. After 4 weeks of 400 ppm, there was a reduction in thymus weight and spleen B-, CD4+/CD5+ and CD5+ T-lymphocytes. Rats exposed to 30, 200 or 400 ppm benzene for 2 or 4 weeks and challenged with sheep red blood cells developed a humoral response comparable to that of the control (0 ppm) animals. Enumeration of spleen T- and B-lymphocytes in rats exposed to benzene and challenged with SRBC showed only a transient reduction in spleen B-lymphocytes after 2 weeks of exposure to 400 ppm. These data suggest that there are no immunotoxicological effects of exposure to 200 ppm benzene or less, in rats exposed for 6 h/day, 5 days/week for 2 or 4 weeks.

  19. A defect in the inflammation-primed macrophage-activation cascade in osteopetrotic rats.

    Science.gov (United States)

    Yamamoto, N; Lindsay, D D; Naraparaju, V R; Ireland, R A; Popoff, S N

    1994-05-15

    Macrophages were activated by administration of lysophosphatidylcholine (lyso-Pc) or dodecylglycerol (DDG) to wild-type rats but not in osteopetrotic (op) mutant rats. In vitro treatment of wild-type rat peritoneal cells with lyso-Pc or DDG efficiently activated macrophages whereas treatment of op mutant rat peritoneal cells with lyso-Pc or DDG did not activate macrophages. The inflammation-primed macrophage activation cascade in rats requires participation of B lymphocytes and vitamin D binding protein (DBP). Lyso-Pc-inducible beta-galactosidase of wild-type rat B lymphocytes can convert DBP to the macrophage-activating factor (MAF), whereas B lymphocytes of the op mutant rats were shown to be deficient in lyso-Pc-inducible beta-galactosidase. DBP is conserved among mammalian species. Treatment of human DBP (Gc1 protein) with commercial glycosidases yields an extremely high titrated MAF as assayed on mouse and rat macrophages. Because the enzymatically generated MAF (GcMAF) bypasses the role of lymphocytes in macrophage activation, the op mutant rat macrophages were efficiently activated by administration of a small quantity (100 pg/rat) of GcMAF. Likewise, in vitro treatment of op rat peritoneal cells with as little as 40 pg GcMAF/ml activated macrophages.

  20. 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.

  1. Antitumor and immune regulation activities of the extracts of some Chinese marine invertebrates

    Institute of Scientific and Technical Information of China (English)

    ZHANG Lixin; FAN Xiao; HAN Lijun

    2005-01-01

    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-lymphocyfes 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 100μg/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.

  2. Cell-specific expression of TLR9 isoforms in inflammation.

    Science.gov (United States)

    McKelvey, Kelly J; Highton, John; Hessian, Paul A

    2011-02-01

    Toll-like receptors (TLRs) are key pattern recognition receptors during an immune response. With five isoforms of human TLR9 described, we hypothesised that differential expression of TLR9 isoforms in different cell types would result in variable contributions to the overall input from TLR9 during inflammation. We assessed the molecular expression of the TLR9 isoforms, TLR9-A, -C and -D. In normal peripheral blood mononuclear cells, B-lymphocytes express ∼100-fold more TLR9-A transcript than monocytes or T-lymphocytes, which predominantly express the TLR9-C transcript. Switches in isoform predominance accompany B-lymphocyte development. TLR9 protein expression in rheumatoid inflammatory lesions reflected the TLR9 isoform expression by immune cells. Herein we suggest that B-lymphocytes and plasmacytoid dendritic cells contribute the ∼3-fold higher TLR9-A transcript levels observed in inflamed synovium when compared to subcutaneous rheumatoid nodules. In contrast, macrophages and T-lymphocytes contribute the ∼4-fold higher TLR9-C transcript levels seen in nodules, compared to synovia. From protein sequence, predictions of subcellular localisation suggest TLR9-B may locate to the mitochondria, whereas TLR9-D adopts an opposing orientation in the endoplasmic reticulum. Consistent with this, structure models raise the possibility of alternative ligands for the TLR9-B and TLR9-D variants. Our results highlight differences in the expression of human TLR9 isoforms in normal and inflamed tissues, with differing contributions to inflammation.

  3. Classical natural ovine scrapie prions detected in practical volumes of blood by lamb and transgenic mouse bioassays.

    Science.gov (United States)

    Dassanayake, Rohana P; Truscott, Thomas C; Zhuang, Dongyue; Schneider, David A; Madsen-Bouterse, Sally A; Young, Alan J; Stanton, James B; Davis, William C; O'Rourke, Katherine I

    2015-01-01

    Scrapie is diagnosed antemortem in sheep by detecting misfolded isoforms of prion protein (PrP(Sc)) in lymphoid follicles of the rectal mucosa and nictitating membranes. Assay sensitivity is limited if (a) the biopsy is collected early during disease development, (b) an insufficient number of follicles is collected, or (c) peripheral accumulation of PrP(Sc) is reduced or delayed. A blood test would be convenient for mass live animal scrapie testing. Currently approved techniques, however, have their own detection limits. Novel detection methods may soon offer a non-animal-based, rapid platform with detection sensitivities that rival the prion bioassay. In anticipation, we sought to determine if diseased animals could be routinely identified with a bioassay using B lymphocytes isolated from blood sample volumes commonly collected for diagnostic purposes in small ruminants. Scrapie transmission was detected in five of six recipient lambs intravenously transfused with B lymphocytes isolated from 5~10 mL of blood from a naturally scrapie-infected sheep. Additionally, scrapie transmission was observed in 18 ovinized transgenic Tg338 mice intracerebrally inoculated with B lymphocytes isolated from 5~10 mL of blood from two naturally scrapie-infected sheep. Based on our findings, we anticipate that these blood sample volumes should be of diagnostic value.

  4. Osteoblastic regulation of B lymphopoiesis is mediated by Gs{alpha}-dependent signaling pathways.

    Science.gov (United States)

    Wu, Joy Y; Purton, Louise E; Rodda, Stephen J; Chen, Min; Weinstein, Lee S; McMahon, Andrew P; Scadden, David T; Kronenberg, Henry M

    2008-11-04

    Osteoblasts play an increasingly recognized role in supporting hematopoietic development and recently have been implicated in the regulation of B lymphopoiesis. Here we demonstrate that the heterotrimeric G protein alpha subunit G(s)alpha is required in cells of the osteoblast lineage for normal postnatal B lymphocyte production. Deletion of G(s)alpha early in the osteoblast lineage results in a 59% decrease in the percentage of B cell precursors in the bone marrow. Analysis of peripheral blood from mutant mice revealed a 67% decrease in the number of circulating B lymphocytes by 10 days of age. Strikingly, other mature hematopoietic lineages are not decreased significantly. Mice lacking G(s)alpha in cells of the osteoblast lineage exhibit a reduction in pro-B and pre-B cells. Furthermore, interleukin (IL)-7 expression is attenuated in G(s)alpha-deficient osteoblasts, and exogenous IL-7 is able to restore B cell precursor populations in the bone marrow of mutant mice. Finally, the defect in B lymphopoiesis can be rescued by transplantation into a WT microenvironment. These findings confirm that osteoblasts are an important component of the B lymphocyte niche and demonstrate in vivo that G(s)alpha-dependent signaling pathways in cells of the osteoblast lineage extrinsically regulate bone marrow B lymphopoiesis, at least partially in an IL-7-dependent manner.

  5. Osteoblastic regulation of B lymphopoiesis is mediated by Gsα-dependent signaling pathways

    Science.gov (United States)

    Wu, Joy Y.; Purton, Louise E.; Rodda, Stephen J.; Chen, Min; Weinstein, Lee S.; McMahon, Andrew P.; Scadden, David T.; Kronenberg, Henry M.

    2008-01-01

    Osteoblasts play an increasingly recognized role in supporting hematopoietic development and recently have been implicated in the regulation of B lymphopoiesis. Here we demonstrate that the heterotrimeric G protein α subunit Gsα is required in cells of the osteoblast lineage for normal postnatal B lymphocyte production. Deletion of Gsα early in the osteoblast lineage results in a 59% decrease in the percentage of B cell precursors in the bone marrow. Analysis of peripheral blood from mutant mice revealed a 67% decrease in the number of circulating B lymphocytes by 10 days of age. Strikingly, other mature hematopoietic lineages are not decreased significantly. Mice lacking Gsα in cells of the osteoblast lineage exhibit a reduction in pro-B and pre-B cells. Furthermore, interleukin (IL)-7 expression is attenuated in Gsα-deficient osteoblasts, and exogenous IL-7 is able to restore B cell precursor populations in the bone marrow of mutant mice. Finally, the defect in B lymphopoiesis can be rescued by transplantation into a WT microenvironment. These findings confirm that osteoblasts are an important component of the B lymphocyte niche and demonstrate in vivo that Gsα-dependent signaling pathways in cells of the osteoblast lineage extrinsically regulate bone marrow B lymphopoiesis, at least partially in an IL-7-dependent manner. PMID:18957542

  6. 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.

  7. [Immunoglobulin genes encoding antibodies directed to oncodevelopmental carbohydrate antigens].

    Science.gov (United States)

    Zenita, K; Yago, K; Fujimoto, E; Kannagi, R

    1990-07-01

    We investigated the immunoglobulin genes which encode the variable region of the monoclonal antibodies directed to the onco-developmental carbohydrate antigens such SSEA-1, fucosyl SSEA-1, SSEA-3 and SSEA-4. The VH region of these antibodies was preferentially encoded by the gene members of the X24, VH7183 and Q52 families, the families which are known to be located at the 3'-end region of the murine germ line VH gene. This result is interesting particularly when considering that the members of the 3'-end VH families are known to be preferentially expressed in embryonic B lymphocytes by an intrinsic genetic program. The comparative study of the nucleic acid sequences of mRNAs encoding these antibodies and the sequences of the corresponding germ line VH genes disclosed that the sequences encoding the antibodies contain no mutation from the germ line VH genes, or contain only a few somatic mutations, which are thought to be insignificant for the reactivity of the antibodies to the nominal antigens. These results imply that some of the embryonic B lymphocytes that express the unmutated germ line VH genes of the 3'-end families can be reactive with embryonic carbohydrate antigens, albeit rearranged with appropriate D-JH gene segments, and coupled with proper light chains. The VH region of the syngenic monoclonal anti-idiotypic antibodies directed to these anti-carbohydrate antibodies were also encoded preferentially by the members of the 3'-end VH families. We propose here that a part of the virgin embryonic B lymphocytes, which express the antibody encoded by the gene members of the 3'-end VH families at the cell surface, will be stimulated by the embryonic carbohydrate antigens which are abundantly present in the internal milieu of the embryo. The clonally expanded B lymphocytes, in turn, will facilitate the proliferation of other populations of embryonic B lymphocytes expressing the corresponding anti-idiotypic antibodies, which are also encoded by the gene members

  8. Effects of fenbendazole on the murine humoral immune system.

    Science.gov (United States)

    Landin, Ana Marie; Frasca, Daniela; Zaias, Julia; Van der Put, Elaine; Riley, Richard L; Altman, Norman H; Blomberg, Bonnie B

    2009-05-01

    Pinworms are highly contagious parasites that have been effectively treated in laboratory rodents with fenbendazole (FBZ). Whether FBZ has any detrimental side effects that may compromise experimental results is unknown. Here we asked whether the immune systems from young and aged mice are altered under FBZ treatment. We compared control and FBZ-treated groups of young (age, 2 to 4 mo) and old (age, 22 to 24 mo) BALB/cN mice. The treated mice received a total of 4 wk (alternating-week treatment regimen) of FBZ-medicated feed. Spleen and bone marrow were collected for immunologic assays, and heart, stomach, intestines, kidneys, and liver were evaluated by histopathology. Our results indicate that FBZ treatment has significant effects on the immune systems of mice; these effects are greater in aged mice. FBZ treatment adversely affected mRNA and protein expression of E2A (a transcription factor crucial for B lymphocytes) in activated precursor B lymphocytes obtained from the bone marrow of young and old mice. These effects were reversed by 6 wk on regular feed after the end of treatment. Activated B lymphocytes from the spleens of young and old mice showed decreased function (cell proliferation, E2A mRNA and protein expression) through the last time point of FBZ treatment but recovered by 2 to 4 wk after treatment. Our findings suggest that FBZ treatment may alter sensitive immune and molecular measures as presented here, and postponing the experimental use of mice until at least 6 wk after treatment should be considered.

  9. Human BLyS facilitates engraftment of human PBL derived B cells in immunodeficient mice.

    Directory of Open Access Journals (Sweden)

    Madelyn R Schmidt

    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.

  10. Peripheral blood lymphocyte HIV DNA levels correlate with HIV associated neurocognitive disorders in Nigeria.

    Science.gov (United States)

    Jumare, Jibreel; Sunshine, Sara; Ahmed, Hayat; El-Kamary, Samer S; Magder, Laurence; Hungerford, Laura; Burdo, Tricia; Eyzaguirre, Lindsay M; Umlauf, Anya; Cherner, Mariana; Abimiku, Alash'le; Charurat, Man; Li, Jonathan Z; Blattner, William A; Royal, Walter

    2017-02-27

    Mononuclear cells play key roles in the pathogenic mechanisms leading to HIV-associated neurocognitive disorders (HANDs). We examined the association between HIV DNA within peripheral blood mononuclear cell (PBMC) subsets and HAND in Nigeria. PBMCs were collected at baseline from 36 antiretroviral naive participants. CD14+ cells and T&B lymphocyte fractions were isolated by, respectively, positive and negative magnetic bead separation. Total HIV DNA within CD14+ and T&B cells were separately quantified using real-time PCR assay targeting HIV LTR-gag and cell input numbers determined by CCR5 copies/sample. Utilizing demographically adjusted T scores obtained from a 7-domain neuropsychological test battery, cognitive status was determined by the global deficit score (GDS) approach, with a GDS of ≥0.5 indicating cognitive impairment. In a linear regression adjusting for plasma HIV RNA, CD4 and lymphocyte count, Beck's depression score, and years of education, there was 0.04 lower log10 HIV DNA copies within T&B lymphocytes per unit increase in global T score (p = 0.02). Adjusting for the same variables in a logistic regression, the odds of cognitive impairment were 6.2 times greater per log10 increase in HIV DNA within T&B lymphocytes (p = 0.048). The association between cognitive impairment and HIV DNA within CD14+ monocytes did not reach statistical significance. In this pretreatment cohort with mild cognitive dysfunction, we found a strong association between levels of HIV DNA within the lymphocyte subset and HAND independent of plasma HIV RNA. These findings likely reflect the neurologic impact of a larger HIV reservoir and active viral replication.

  11. 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.

  12. Polymorphisms of the SAMHD1 Gene Are Not Associated with the Infection and Natural Control of HIV Type 1 in Europeans and African-Americans

    Science.gov (United States)

    Coon, Sirena; Wang, Danxin

    2012-01-01

    Abstract The HIV-1 restriction factor SAM domain and HD domain-containing protein 1 (SAMHD1) blocks HIV-1 infection in human myeloid cells. Mutations in the SAMHD1 gene are associated with rare genetic diseases including Aicardi–Goutieres syndrome. However, it is unknown whether polymorphisms of SAMHD1 are associated with infection and natural control of HIV-1 in humans. Our objective was to determine whether the expression of SAMHD1 mRNA is affected by common single nucleotide polymorphisms (SNPs) in SAMHD1 and whether the SNPs are associated with HIV-1 infection status. Using a tagging SNP approach, we determined the association between eight tagging SNPs in SAMHD1 and the mRNA expression in B-lymphocyte cell lines from 70 healthy white donors. We identified one SNP (rs1291142) that was significantly associated with SAMHD1 mRNA expression, with minor allele carriers having 30% less mRNA levels (p=0.015). However, after analyzing the published genome-wide association study data of 857 HIV-1 controllers and 2088 HIV-1 progressors from the European and African-American cohorts, we did not find a significant association between SNPs in SAMHD1 and HIV-1 infection status, including SNP rs1291142 (p>0.05). We also observed 2- to 6-fold variations of SAMHD1 mRNA levels in primary B-lymphocytes, CD4+ T-lymphocytes, and CD14+ monocytes from five healthy donors. Our results suggest that common regulatory polymorphism(s) exist in the SAMHD1 gene that affects its mRNA expression in B-lymphocyte cell lines from healthy whites. However, polymorphisms of SAMHD1 are unlikely to contribute to the infection and natural control of HIV-1 in European and African-American individuals. PMID:22530776

  13. Abnormal B-cell activation associated with TALL-1 over-expression and SOCS-1 suppression during chronic hepatitis C virus infection.

    Science.gov (United States)

    Moorman, Jonathan; Dong, Zhi P; Ni, Lei; Zhang, Chunlan; Borthwick, Thomas; Yao, Zhi Q

    2009-10-01

    Chronic hepatitis C virus (HCV) infection is associated with cirrhosis, autoimmunity and lymphoproliferative disorders. We have previously reported a differential regulation of T and B lymphocytes by HCV core protein in vitro. In this report, we employed a translational approach to characterize the activation status of peripheral B cells from individuals with chronic HCV infection and to explore potential mechanisms for B-cell dysregulation in the setting of HCV infection. In contrast to the T-cell suppression observed in HCV-infected individuals, B cells exhibit a non-specific polyclonal activation phenotype, characterized by significantly higher levels of (1) the early activation marker, CD69, (2) the costimulatory molecule, CD86, and (3) the CCR5 chemokine receptor, CD195, when compared with B cells from healthy donors in response to phytohaemagglutinin (PHA) stimulation. Importantly, tumour necrosis factor- and Apo-L-related leucocyte-expressed ligand-1 (TALL-1), also known as B-lymphocyte stimulator (BLYS), was found to be up-regulated on the surface of B cells from HCV patients in response to PHA as well as HCV core antigen stimulation. This up-regulation of TALL-1 was associated with vigorous memory B-cell responses to viral antigenic stimulation. Additionally, suppressor of cytokine signalling-1 (SOCS-1), a negative feedback immunoregulator that is inhibited in B lymphocytes by HCV core in vitro, was also inhibited in B cells from HCV patients when compared with healthy donors. These findings suggest that TALL-1 over-expression and SOCS-1 suppression are associated with aberrant B-cell activation, providing a plausible basis for the B-cell clonal expansion underlying the lymphoproliferative disorders and autoimmune phenomena observed during chronic HCV infection.

  14. 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.

  15. Immune reactions and nerve repair in mice with sciatic nerve injury 14 days after intraperitoneal injection of Brazil

    Institute of Scientific and Technical Information of China (English)

    Jian Cao; Zhongping Niu; Yongan Wang; Yiwen Jiang; Haoyu Liu; Binfeng Wang; Weitian Yin; Lisen Li

    2012-01-01

    BALB/c mice were intraperitoneally injected with 10, 5 or 2.5 mg/kg Brazil for 14 days after sciatic nerve injury. Results demonstrate that the spleen T/B lymphocyte stimulation index and serum circulating immune complex concentration were significantly reduced, and the morphology of the soleus muscle was restored in mice with sciatic nerve injury. These effects of Brazil were dose-dependent. Our experimental findings indicate that Brazil can regulate immune responses after nerve injury and promote sciatic nerve repair.

  16. The POLD3 subunit of DNA polymerase δ can promote translesion synthesis independently of DNA polymerase ζ

    OpenAIRE

    Hirota, Kouji; Yoshikiyo, Kazunori; Guilbaud, Guillaume; Tsurimoto, Toshiki; Murai, Junko; Tsuda, Masataka; Phillips, Lara G.; Narita, Takeo; Nishihara, Kana; Kobayashi, Kaori; Yamada, Kouich; Nakamura, Jun; Pommier, Yves; Lehmann, Alan; Sale, Julian E.

    2015-01-01

    The replicative DNA polymerase Polδ consists of a catalytic subunit POLD1/p125 and three regulatory subunits POLD2/p50, POLD3/p66 and POLD4/p12. The ortholog of POLD3 in Saccharomyces cerevisiae, Pol32, is required for a significant proportion of spontaneous and UV-induced mutagenesis through its additional role in translesion synthesis (TLS) as a subunit of DNA polymerase ζ. Remarkably, chicken DT40 B lymphocytes deficient in POLD3 are viable and able to replicate undamaged genomic DNA with ...

  17. Chimerism in a child with severe combined immunodeficiency: a case report.

    Science.gov (United States)

    Aureli, Anna; Piancatelli, Daniela; Monaco, Palmina I; Ozzella, Giuseppina; Canossi, Angelica; Piazza, Antonina; Isacchi, Giancarlo; Caniglia, Maurizio; Adorno, Domenico

    2006-09-01

    Severe combined immunodeficiency (SCID) represents a group of rare, sometimes fatal, congenital disorders in which there is a combined absence of T-lymphocyte and B-lymphocyte function. Children with SCID die within two years of age, if untreated. The effective treatment for SCID is a hematopoietic stem cell transplantation (HSCT). It has been repeatedly described that in peripheral blood of infants with SCID maternal T cells can be found. Here we report a case of blood chimerism in a one-year-old boy with SCID.

  18. Influence of immunomodulators of natural origin on cellular immunity indices in blood of broiler chicken under stress

    Directory of Open Access Journals (Sweden)

    S. Grabovskyi

    2015-03-01

    Full Text Available The paper deals with researching of T- and B-lymphocytes relative quantity and functional activity in broiler chicken blood after using of animal origin immunomodulators in conditions of pre-slaughter stress. The authors determined the relative amount of T- and B-lymphocytes and their individual populations in the reaction of spontaneous rоsetting with the sheep erythrocytes in blood. Besides, the differentiated count of rоsetting lymphocytes with the various degree of functional activity was conducted. The spleen extract (70% alcohol solution in volume of 1.4 ml per chicken was added to the diet of broiler chicken of experimental groups by aerosol method. This extract was obtained with/ without ultrasound application. 70% alcohol solution in the same volume and using the same method was added to the diet of broiler chicken of the control group five days before slaughter. The authors have not established probable increase of T-lymphocytes general quantity in broiler chicken blood in both experimental groups. It is shown that pre-slaughter stress in broiler chicken caused by weaning has immuno-suppressive effect on T- and B-lymphocytes in blood, which is accompanied by their quantity and functional activity decrease. T- and B-lymphocytes amount and functional activity of T- and B-cell immunity was stimulated after adding immunomodulators of natural origin to broiler chicken diet. Spleen extract polyamines as immunomodulators and antistressors most effectively influenced on some of cell immunity indices before slaughter – it is necessary to note the increase in T-helper lymphocytes in the broiler chickens blood caused by lymphocytes with medium (6–10 – by 18% (Р < 0.05 and high density receptors (М – by 35% (Р < 0.05 compared to the control. It is shown that decrease of T-lymphocytes quantity in broiler chicken blood is caused by lymphocytes with law (3–5 – by 22% (Р < 0.01 and high (M – by 11% (Р < 0.05 density receptors with

  19. V(D)J recombination in mature B cells: a mechanism for altering antibody responses.

    Science.gov (United States)

    Papavasiliou, F; Casellas, R; Suh, H; Qin, X F; Besmer, E; Pelanda, R; Nemazee, D; Rajewsky, K; Nussenzweig, M C

    1997-10-10

    The clonal selection theory states that B lymphocytes producing high-affinity immunoglobulins are selected from a pool of cells undergoing antibody gene mutation. Somatic hypermutation is a well-documented mechanism for achieving diversification of immune responses in mature B cells. Antibody genes were also found to be modified in such cells in germinal centers by recombination of the variable (V), diversity (D), and joining (J) segments. The ability to alter immunoglobulin expression by V(D)J recombination in the selective environment of the germinal center may be an additional mechanism for inactivation or diversification of immune responses.

  20. The T-box Transcription Factor T-bet in Immunity and Autoimmunity

    Institute of Scientific and Technical Information of China (English)

    Stanford L. Peng

    2006-01-01

    The T-box transcription factor T-bet (Tbx21) has emerged as a key regulator of type 1-like immunity, playing critical roles in the establishment and/or maintenance of effector cell fates in T and B lymphocytes, as well as dendritic cells and natural killer cells. Several autoimmune diseases, especially those classically considered related to T helper 1 (Th1) immunity, appear to require T-bet, at least as judged in mouse models. This review summarizes a current understanding of T-bet's role in immunity, as well as its importance in autoimmunity, with implications for therapeutic intervention.

  1. Interactome maps of mouse gene regulatory domains reveal basic principles of transcriptional regulation

    DEFF Research Database (Denmark)

    Kieffer-Kwon, Kyong-Rim; Tang, Zhonghui; Mathe, Ewy

    2013-01-01

    IA-PET technologies to map the promoter-enhancer interactomes of pluripotent ES cells and differentiated B lymphocytes. We confirm that enhancer usage varies widely across tissues. Unexpectedly, we find that this feature extends to broadly transcribed genes, including Myc and Pim1 cell-cycle regulators, which...... associate with an entirely different set of enhancers in ES and B cells. By means of high-resolution CpG methylomes, genome editing, and digital footprinting, we show that these enhancers recruit lineage-determining factors. Furthermore, we demonstrate that the turning on and off of enhancers during...

  2. 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.

  3. [Primary Meckel's cave lymphoma. A case and review of the literature].

    Science.gov (United States)

    Artico, M; Salvati, M; Raco, A; Innocenzi, G; Delfini, R

    1992-01-01

    A rare case of Meckel's cavity lymphoma is presented. Only two other cases of identical localization have been presented in the literature. The symptoms consisted of sensorimotor impairment of the Vth nerve associated with slight exophthalmos. C.T. scan showed a hyperdense lesion in Meckel's cavity. After total surgical removal, histological analysis diagnosed a B-lymphocyte non-Hodgkin's lymphoma. The patient received both radiotherapy and chemotherapy and at one year follow up, the clinical course was good. The lesion had no clinical or radiological specificity. Its prognosis appears to be identical to that of other intracranial lymphomas.

  4. The spliced BZLF1 gene of Epstein-Barr virus (EBV) transactivates an early EBV promoter and induces the virus productive cycle.

    OpenAIRE

    1989-01-01

    A spliced cDNA spanning the Epstein-Barr virus BZLF1 gene expresses the BZLF1 protein and is active in inducing the virus productive cycle. A deletion mutant which lacks the N-terminal half of the protein is inactive. Cotransfection experiments in EBV-negative B-lymphocyte cell lines demonstrated that the BZLF1 gene activates the promoter for the BSLF2 + BMLF1 gene in the absence of any other EBV gene product. These results confirmed that the spliced BZLF1 gene is the transactivating gene str...

  5. [Clinical and experimental research of immunomodulatory effect of amisulpride].

    Science.gov (United States)

    Vetlugina, T P; Lobacheva, O A; Al'perina, E L; Zhukova, E N; Semke, A V; Nikitina, V B; Cheĭdo, M A; Idova, G V

    2012-01-01

    Study of immunomodulatory effect of atypical antipsychotic amisulpride has revealed a positive clinical effect after 6-week therapy of schizophrenic patients regarding both positive and negative symptoms. A decrease in activity of humoral immunity factors (B lymphocytes, immunoglobulins, HLADR(+)-cells) identified among schizophrenic patients in the process of amisulpride therapy can be attributed to a positive effect optimizing the ratio Th1/Th2. Amisulpride when used under experimental conditions produced a suppression of IgM-immune response in mice of the C57BL/6J strain. This effect was more expressed in animals with aggressive behavior pattern.

  6. Summaries of Research 1986

    Science.gov (United States)

    1986-01-01

    LEUKOSIS VIRUSES AVIAN LEUKOSIS B LYMPHOCYTES SURSA OF FABRICIUS CELL TRANSFORMATION, NEOPLASTIC CHICKENS LYMPHOMA AD A177 613 NMRP 96-0079 LEDBETTER...AD A166 309 NMRI 86-0004 SHAPER NL SHAPER JH MZUTH JL FOX JL CHANG 8 KIRSCH If HOLLIS GF BOVINE GALACTOSYLTRANSFERASE: IDENTIFICATION OF A CLONE BY...1986 JUL;124(1):111-3 LIMA DETACHMENT 3MI62770A870.AB.127 REPORT NO.3 ANTIBODIES, VIRAL HEPATITIS A VIRUS HEPATITIS A IGN AD A171 q5 6 NhMI 86-0047

  7. Identification of a protein that interacts with the nuclear factor-1 (NF-1) binding site in cells that do not express NF-1: comparison to NF-1, cellular distribution, and effect on transcription.

    OpenAIRE

    McQuillan, J J; Rosen, G.D.; Birkenmeier, T M; Dean, D C

    1991-01-01

    We examined expression of nuclear factor-1 (NF-1) in different cell lines. Expression was low or undetectable in T and B lymphocyte cell lines, whereas fibroblasts and other adherent cell lines generally had a relatively high level of NF-1 mRNA. In cell lines that did not express NF-1, gel retardation assays, nevertheless, indicated complexes between a protein or proteins and the NF-1 site. These complexes were less abundant than those formed with NF-1, they migrated more slowly, and they app...

  8. Three monoclonal antibodies to the VHS virus glycoprotein: comparison of reactivity in relation to differences in immunoglobulin variable domain gene sequences

    DEFF Research Database (Denmark)

    Lorenzen, Niels; Cupit, P.M.; Secombes, C.J.;

    2000-01-01

    Three monoclonal antibodies (MAbs) to the VHSV G protein were compared in different immunoassays and the variable domain cDNA sequences from the respective immunoglobulin (Ig) genes were determined. One MAb (IP1H3) was non-neutralising and recognised different virus isolates equally well in ELISA...... originated from the same virgin B lymphocyte. The few differences observed in the VH and V kappa amino acid sequences were probably due to somatic mutations arising during affinity maturation and might explain the observed reactivity differences between the two MAbs....

  9. Use of the immunomodulative influence of low-level laser radiation in the treatment of an autoimmune thyroiditis

    Science.gov (United States)

    Mikhailov, V. A.; Alexandrova, O. A.; Denisov, I. N.

    2000-06-01

    Use of LLLT for 42 patients with an autoimmune thyroiditis has shown that the helper function of lymphocytes has decreased, the suppressive activity has increased, the quantity of B-lymphocytes has decreased and the immunoregulative index has been normalized. The effect of LLLT application was active about 4 months in 78 percent of the patients. Soft semiconductor laser was used. The radiation was in the IR range of spectrum, wavelength - 890 nm. The technique included cutaneous irradiation of the thymus projection zones, vascular junction and thyroid gland. The total doze was made 2.42 J/cm2.

  10. Cellular choreography in the germinal center: new visions from in vivo imaging.

    Science.gov (United States)

    Hauser, Anja E; Kerfoot, Steven M; Haberman, Ann M

    2010-09-01

    Germinal centers (GC) are large aggregates of proliferating B lymphocytes within follicles of lymphoid tissue that form during adaptive immune responses. GCs are the source of long-lived B cells that form the basis for pathogen-specific lifelong B cell immunity. The complex architecture of these structures includes subdomains that differ significantly in their stromal cell and T lymphocyte subset composition. In part due to their structural complexity and potential to generate some lymphomas, much interest and many theories about GC dynamics have emerged. Here, we review recent research employing in vivo imaging that has begun to untangle some of the mysteries.

  11. Association of Acromegaly and Multiple Myeloma: A Case Report

    Directory of Open Access Journals (Sweden)

    Murat Atmaca

    2013-09-01

    Full Text Available Malignancy is an important cause of mortality in acromegaly. Hematological malignancies are very rare in acromegaly. Here, we report an 80-year-old patient with acromegaly and multiple myeloma. Patient died within a month of diagnosis. Previous studies have shown that growth hormone and somatomedin-C activate B lymphocyte and somatomedin-C receptors are found in multiple myeloma cells. Possible effects of growth hormone and somatomedin-C on multiple myeloma progression are discussed in the light of the relevant literature. Turk Jem 2013; 17: 75-7

  12. 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.

  13. 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.

  14. Organization of immunoglobulin genes.

    Science.gov (United States)

    Tonegawa, S; Brack, C; Hozumi, N; Pirrotta, V

    1978-01-01

    The nucleotide-sequence determination of a cloned, embryonic Vlambda gene directly demonstrated that V genes are separate from a corresponding C gene in embryonic cells. Analysis by restriction enzymes of total cellular DNA from various sources strongly suggested that the two separate immunoglobulin genes become continuous during differentiation of B lymphocytes. There seems to be a strict correlation between the joining event and activation of the joined genes. Cloning of more immunoglobulin genes from embryo and plasma cells will not only provide direct demonstration of such a gene-joining event but also help in the elucidation of a possible relationship of the event to gene activation mechanisms.

  15. 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

    -specific antibody-secreting cells (AbSC) of the isotypes IgM, IgG, and IgA. The appearance of AbSC in the blood after vaccination of adults with diphtheria toxoid-conjugated Hib polysaccharide was investigated. AbSC were detected from post-vaccination day 5 to day 14. IgA was the predominant isotype among......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...

  16. Life and death of lymphocytes: a role in immunesenescence

    Directory of Open Access Journals (Sweden)

    Agrawal Sudhanshu

    2005-08-01

    Full Text Available Abstract Human aging is associated with progressive decline in immune functions, increased frequency of infections. Among immune functions, a decline in T cell functions during aging predominates. In this review, we will discuss the molecular signaling in two major pathways of apoptosis, namely death receptor pathway and mitochondrial pathway, and their alterations in both T and B lymphocytes in human aging with a special emphasis on naïve and different memory subsets of CD8+ T cells. We will also discuss a possible role of lymphocyte apoptosis in immune senescence.

  17. Study of cell classification with a diffraction imaging flow cytometer method

    Science.gov (United States)

    Dong, Ke; Jacobs, Kenneth M.; Sa, Yu; Feng, Yuanming; Lu, Jun Q.; Hu, Xin-Hua

    2011-02-01

    With a diffraction imaging flow cytometer, we have acquired and analyzed the diffraction imaging data from 5 types of cultured cells. A gray level co-occurrence matrix (GLCM) algorithm was applied to extract the interference fringe related textures from the diffraction image data. Six GLCM parameters were chosen and imported into a support vector machine algorithm for automated classification of about 20 cells for each of the 5 cell types. We found that the GLCM based algorithm has the capacity for rapid processing of diffraction images and yield feature parameters for subsequent cell classification except the T- and B-lymphocytes.

  18. [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.

  19. 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 a two-week interval and in combination with methotrexate. Mild to moderate side-effects are frequent, particularly during the first infusion, but long-term side-effects are generally rare, although pulmonary events and reactivation of viral infections of the liver is of concern....

  20. Adhesion of Human B Cells to Germinal Centers in Vitro Involves VLA-4 and INCAM-110

    Science.gov (United States)

    Freedman, Arnold S.; Munro, J. Michael; Rice, G. Edgar; Bevilacqua, Michael P.; Morimoto, Chikao; McIntyre, Bradley W.; Rhynhart, Kurt; Pober, Jordan S.; Nadler, Lee M.

    1990-08-01

    Human B lymphocytes localize and differentiate within the microenvironment of lymphoid germinal centers. A frozen section binding assay was developed for the identification of those molecules involved in the adhesive interactions between B cells and lymphoid follicles. Activated human B cells and B cell lines were found to selectively adhere to germinal centers. The VLA-4 molecule on the lymphocyte and the adhesion molecule INCAM-110, expressed on follicular dendritic cells, supported this interaction. This cellular interaction model can be used for the study of how B cells differentiate.

  1. Massive ascites as a presenting manifestation of chronic lymphocytic leukemia

    Institute of Scientific and Technical Information of China (English)

    Neelam Siddiqui; Saeed Al-Amoudi; Aamer Aleem; Maha Arafah; Layla Al-Gwaiz

    2008-01-01

    Ascites is not an uncommon manifestation of certain solid tumors like gastrointestinal malignancies, ovarian cancer and breast cancer. However, it is unusual to encounter ascites in patients with hematological malignancies especially chronic leukemia. The patient described here presented with massive ascites and blood lymphocytosis. Further studies confirmed the diagnosis of chronic lymphocytic leukemia with ascites. The ascitic fluid was exudative, consisting of mature-looking B-lymphocytes, which were morphologically and immunophenotypically similar to peripheral blood and bone marrow cells. The patient was treated with chemotherapy and achieved a good response and diminution of ascitic fluid accumulation.

  2. A Review of Clinical Trials of Belimumab in the Management of Systemic Lupus Erythematosus.

    Science.gov (United States)

    Garcia, Alexis; De Sanctis, Juan B

    2016-01-01

    There have been few changes over the last 50 years in the treatment of Systemic lupus erythematosus (SLE), using non-specific anti-inflammatory agents such as: nonsteroidal anti-inflammatory drugs along with the immune cell modulating agent hydroxychloroquine for mild disease, and broad spectrum immunosuppressants plus antiinflammatories such as corticosteroids, azathioprine, cyclophosphamide, or mycophenolate during flares or severe disease with organ involvement. In some patients, the response is inadequate and side effects appear from mild unpleasant up to severe toxicity. Drug metabolism and clearance may be severely compromised. Therefore, it is a priority to develop better treatments with fewer adverse events that can be used at different stages of disease activity. In recent years, a member of the tumor necrosis factor (TNF) family, soluble human B Lymphocyte Stimulator protein (BLyS), also referred to as B-cell activating factor (BAFF) and TNFSF13B has been studied extensively. This protein is synthesized by myeloid cell lines, specifically interacts with B lymphocytes and increases their life-span. BlyS plays a key role in the selection, maturation and survival of B cells and it has a significant role in the pathogenesis of SLE. In this review, we analyzed the role of BLyS as a diagnostic/prognostic marker and/or therapeutic target for lupus patients, and the different clinical studies published using belimumab.

  3. Immunophenotypic lymphocyte profiles in human african trypanosomiasis.

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    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.

  4. Homeostatic 'bystander' proliferation of human peripheral blood B cells in response to polyclonal T-cell stimulation in vitro.

    Science.gov (United States)

    Jasiulewicz, Aleksandra; Lisowska, Katarzyna A; Pietruczuk, Krzysztof; Frąckowiak, Joanna; Fulop, Tamas; Witkowski, Jacek M

    2015-11-01

    The mechanisms of maintenance of adequate numbers of B lymphocytes and of protective levels of immunoglobulins in the absence of antigenic (re)stimulation remain not fully understood. Meanwhile, our results presented here show that both peripheral blood naive and memory B cells can be activated strongly and non-specifically (in a mitogen-like fashion) in 5-day in vitro cultures of anti-CD3- or concanavalin A (Con A)-stimulated peripheral blood mononuclear cells of healthy people. This polyclonal, bystander activation of the B cells includes multiple divisions of most of them (assessed here by the flow cytometric technique of dividing cell tracking) and significant antibody [immunoglobulin M (IgM) and IgG] secretion. Observed proliferation of the CD19(+) B cells depends on contact with stimulated T helper (Th) cells (via CD40-CD40L interaction) and on the response of B cells to secreted interleukins IL-5, IL-10 and IL-4, and is correlated with the levels of these Th-derived molecules, while it does not involve the ligation of the BCR/CD19 complex. We suggest that the effect might reflect the situation occurring in vivo as the homeostatic proliferation of otherwise non-stimulated, peripheral B lymphocytes, providing an always ready pool for efficient antibody production to any new (or cognate) antigen challenge.

  5. Evaluation of T, B and natural killer lymphocyte in the cervical stroma of HIV-positive and negative patients with cervical intraepithelial neoplasia.

    Science.gov (United States)

    Lucena, Adriana A S; Guimarães, Mírian Viviane M B; Michelin, Márcia A; Lodi, Cláudia T C; Lima, Maria Inês M; Murta, Eddie Fernando Candido; Melo, Victor Hugo

    2016-01-01

    Cervical intraepithelial neoplasias (CIN) are closely associated with oncogenic subtypes of the human papillomavirus (HPV). In the presence of this virus, it is known that the activation or suppression of immune system is the key to the development, progression and/or regression of cervical lesions. Therefore, the objective of this study is to compare the local immune response among HIV-seropositive and seronegative patients with cervical intraepithelial neoplasia regarding the expression of T lymphocytes (CD3+, CD4+ and CD8+), B lymphocytes (CD20+) and natural killers cells (CD56+) in the cervical stroma. A cross-sectional study of paraffin blocks containing cervical tissue after conization by the Loop Electrosurgical Excision Procedure (LEEP) from 47 HIV-seropositive and 38 seronegative patients with CIN. Cervical stroma immunohistochemistry was performed in the CIN area. The Fisher's exact test was used for the statistical analysis. When HIV-seropositive and seronegative women were compared, the seropositive women had a higher count of CD8+ T lymphocytes (52.1% versus 28.9%, PHIV-seronegative patients with CIN 1 had a low count of CD20+B-lymphocytes (7.1%) in comparison with CIN 1 HIV seropositive and with CIN 2/3 HIV-seronegative patients, respectively 50% (PHIV infection and degree of CIN influenced the cytotoxic lymphocytes inducing an increase in the number of cells high count of CD20+ lymphocytes with CIN 1.

  6. Germinal centre protein HGAL promotes lymphoid hyperplasia and amyloidosis via BCR-mediated Syk activation.

    Science.gov (United States)

    Romero-Camarero, Isabel; Jiang, Xiaoyu; Natkunam, Yasodha; Lu, Xiaoqing; Vicente-Dueñas, Carolina; Gonzalez-Herrero, Ines; Flores, Teresa; Garcia, Juan Luis; McNamara, George; Kunder, Christian; Zhao, Shuchun; Segura, Victor; Fontan, Lorena; Martínez-Climent, Jose A; García-Criado, Francisco Javier; Theis, Jason D; Dogan, Ahmet; Campos-Sánchez, Elena; Green, Michael R; Alizadeh, Ash A; Cobaleda, Cesar; Sánchez-García, Isidro; Lossos, Izidore S

    2013-01-01

    The human germinal centre-associated lymphoma gene is specifically expressed in germinal centre B-lymphocytes and germinal centre-derived B-cell lymphomas, but its function is largely unknown. Here we demonstrate that human germinal centre-associated lymphoma directly binds to Syk in B cells, increases its kinase activity on B-cell receptor stimulation and leads to enhanced activation of Syk downstream effectors. To further investigate these findings in vivo, human germinal centre-associated lymphoma transgenic mice were generated. Starting from 12 months of age these mice developed polyclonal B-cell lymphoid hyperplasia, hypergammaglobulinemia and systemic reactive amyloid A (AA) amyloidosis, leading to shortened survival. The lymphoid hyperplasia in the human germinal centre-associated lymphoma transgenic mice are likely attributable to enhanced B-cell receptor signalling as shown by increased Syk phosphorylation, ex vivo B-cell proliferation and increased RhoA activation. Overall, our study shows for the first time that the germinal centre protein human germinal centre-associated lymphoma regulates B-cell receptor signalling in B-lymphocytes which, without appropriate control, may lead to B-cell lymphoproliferation.

  7. Effects of dietary Fusarium mycotoxins on intestinal lymphocyte subset populations, cell proliferation and histological changes in avian lymphoid organs.

    Science.gov (United States)

    Girish, C K; Smith, T K; Boermans, H J; Anil Kumar, P; Girgis, G N

    2010-10-01

    An experiment was conducted to investigate the effects of dietary Fusarium mycotoxins on gut immunity, cell proliferation, and histology of avian lymphoid organs. The efficacy of a polymeric glucomannan mycotoxin adsorbent (GMA) was also determined. Seventy-two one-day-old male turkey poults were fed corn, wheat, and soybean meal-based diets for 21 days. Diets included control grains, contaminated grains and contaminated grains +0.2% GMA. The major contaminant was deoxynivalenol (3.9 μg/g) with lesser amounts of zearalenone (0.67-0.75 μg/g), 15-acetyl-deoxynivalenol (0.34 μg/g) and HT-2 toxin (0.078-0.085 μg/g). T- and B-lymphocyte populations and crypt cellular proliferation in duodenum, jejunum, ileum and cecal tonsil were measured immunohistochemically on day 14 and 21. Histological changes were recorded after 14 and 21 days of feeding. Feeding contaminated grains significantly increased the percentage of B-lymphocytes in ileum on day 14, and reduced (Pcontaminated diets also caused a reduction (Pcontaminated with Fusarium mycotoxins results in adverse effects on gut immunity and mucosal cell proliferation.

  8. Lymphocyte subset reference intervals in blood donors from northeastern Brazil

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    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.

  9. Position of chromosomes 18, 19, 21 and 22 in 3D-preserved interphase nuclei of human and gorilla and white hand gibbon

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    Bhatt Samarth

    2008-04-01

    Full Text Available Abstract Background Even though comparative nuclear architecture studies in hominoids are sparse, nuclear chromosome architecture was shown to be conserved during hominoid evolution. Thus, it is suspected that yet unknown biological mechanisms must underlie this observation. Results Here for the first time a combination of multicolor banding (MCB and three-dimensional analysis of interphase cells was used to characterize the position and orientation of human chromosomes #18, #19, #21 and #22 and their homologues in primate B-lymphocytic cells. In general, our data is in concordance with previous studies. The position of the four studied human chromosomes and their homologues were conserved during primate evolution. However, comparison of interphase architecture in human B-lymphocytic cells and sperm revealed differences of localization of acrocentric chromosomes. The latter might be related to the fact that the nucleolus organizing region is not active in sperm. Conclusion Studies in different tissue types may characterize more – potentially biologically relevant differences in nuclear architecture.

  10. Functional interaction of caveolin-1 with Bruton's tyrosine kinase and Bmx.

    Science.gov (United States)

    Vargas, Leonardo; Nore, Beston F; Berglof, Anna; Heinonen, Juhana E; Mattsson, Pekka T; Smith, C I Edvard; Mohamed, Abdalla J

    2002-03-15

    Bruton's tyrosine kinase (Btk), a member of the Tec family of protein-tyrosine kinases, has been shown to be crucial for B cell development, differentiation, and signaling. Mutations in the Btk gene lead to X-linked agammaglobulinemia in humans and X-linked immunodeficiency in mice. Using a co-transfection approach, we present evidence here that Btk interacts physically with caveolin-1, a 22-kDa integral membrane protein, which is the principal structural and regulatory component of caveolae membranes. In addition, we found that native Bmx, another member of the Tec family kinases, is associated with endogenous caveolin-1 in primary human umbilical vein endothelial cells. Second, in transient transfection assays, expression of caveolin-1 leads to a substantial reduction in the in vivo tyrosine phosphorylation of both Btk and its constitutively active form, E41K. Furthermore, a caveolin-1 scaffolding peptide (amino acids 82--101) functionally suppressed the autokinase activity of purified recombinant Btk protein. Third, we demonstrate that mouse splenic B-lymphocytes express substantial amounts of caveolin-1. Interestingly, caveolin-1 was found to be constitutively phosphorylated on tyrosine 14 in these cells. The expression of caveolin-1 in B-lymphocytes and its interaction with Btk may have implications not only for B cell activation and signaling, but also for antigen presentation.

  11. Receptor activator of nuclear factor kappa B ligand and osteoprotegerin expression in chronic apical periodontitis:possible association with inflammatory cells

    Institute of Scientific and Technical Information of China (English)

    FAN Rong; SUN Bin; ZHANG Cheng-fei; L(U) Ya-lin; XUAN Wei; WANG Qian-qian; YIN Xing-zhe

    2011-01-01

    Background Receptor activator of nuclear factor kappa B (NF-κB) ligand (RANKL) and osteoprotegerin (OPG) have been recently shown to play important roles in bone resorption. The aim of this study was to investigate the possible association between the expression of bone resorption regulators (RANKL and OPG) and inflammatory cell infiltration in chronic apical periodontitis.Methods The samples of chronic periapical lesions (n=40) and healthy periapical tissues (n=10) were examined for immunohistochemical analysis of RANKL and OPG. Lesion samples were further analyzed for the inflammatory infiltration condition. The inflammatory cell infiltration was scored in relation to immunohistochemical reactivity for CD3, CD20 and CD68.Results The number of RANKL-positive cells and the ratio of RANKL/OPG in chronic apical periodontitis were significantly higher than those in healthy periapical tissues (P<0.001). The number of RANKL-positive cells was higher in lesions with severe inflammatory infiltration than in those with light inflammatory infiltration (P<0.05). Significantly increased RANKL expression was found with T lymphocytes (CD3+), macrophages (CD68+) and B lymphocytes (CD20+)infiltration (P<0.05). No association was found between the ratio of RANKL/OPG and inflammatory cell infiltration.Conclusions RANKL expression was increased with T, B lymphocytes and macrophages infiltration, respectively in chronic periapical lesions. RANKL appears to be closely related to periapical inflammatory infiltrates. The relative ratio of RANKL/OPG may be a key determinant of RANKL-mediated bone resorption.

  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.

  13. Distribution of immunocompetent cells in the lungs of premature newborns on the background of some components of mother metabolic syndrome

    Directory of Open Access Journals (Sweden)

    Rudyak O.M.

    2011-01-01

    Full Text Available In immunohistochemical researching of the local immune system of the lungs (90 premature newborns, 29-33 weeks gestation, divided into 3 groups with respect to the components of mothers metabolic syndrome , the features and patterns of distribution, quantitative indicators of immune cells in the bronchial and respiratory departments are detected. It was determined that children who belong to group №1 (mothers hypertension and dyslipidemia have the total depression of T-lymphocytes (CD3, reduction of helper function (CD4, mixed reaction of suppressors (CD8, decreasing the number of B-lymphocytes - subpopulations (CD20, inhibition of macrophagic function (CD68. In group№2 (mothers diabetes type 2 and dyslipidemia we observed depression of helper-suppressor functions (CD4, CD8, increasing of macrophagic reaction (CD68. Reducing of the absolute number of suppressor and cytotoxic T-lymphocytes subpopulations, a decreasing of B-lymphocytes (CD20 and inhibition of macrophagic functions (CD68 is observed in group№3 of children at the background of mothers adiposity and dyslipidemia. Reducing of expression of CD3 lymphocytes and levels of CD4 cells shows intensive reaction of cellular immunity in premature newborns. Comparative analysis of the immune status of the lungs of children in three groups with different components of mothers metabolic syndrome shows an acute disbalance of immunoregulation index, and the negative impact of mothers disease on histogenetic processes of respiratory organization.

  14. Epstein-Barr virus nuclear antigen 2 specifically induces expression of the B-cell activation antigen CD23

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    Wang, F.; Gregory, C.D.; Rowe, M.; Rickinson, A.B.; Wang, D.; Birkenbach, M.; Kikutani, H.; Kishimoto, T.; Kieff, E.

    1987-05-01

    Epstein-Barr virus (EBV) infection of EBV-negative Burkitt lymphoma (BL) cells includes some changes similar to those seen in normal B lymphocytes that have been growth transformed by EBV. The role of individual EBV genes in this process was evaluated by introducing each of the viral genes that are normally expressed in EBV growth-transformed and latently infected lymphoblasts into an EBV-negative BL cell line, using recombinant retrovirus-mediated transfer. Clones of cells were derived that stably express the EBV nuclear antigen 1 (EBNA-1), EBNA-2, EBNA-3, EBNA-leader protein, or EBV latent membrane protein (LMP). These were compared with control clones infected with the retrovirus vector. All 10 clones converted to EBNA-2 expression differed from control clones or clones expressing other EBV proteins by growth in tight clumps and by markedly increased expression of one particular surface marker of B-cell activation, CD23. Other activation antigens were unaffected by EBNA-2 expression, as were markers already expressed on the parent BL cell line. The results indicate that EBNA-2 is a specific direct or indirect trans-activator of CD23. This establishes a link between an EBV gene and cell gene expression. Since CD23 has been implicated in the transduction of B-cell growth signals, its specific induction by EBNA-2 could be important in EBV induction of B-lymphocyte transformation.

  15. Complement Receptor Type 1 Suppresses Human B Cell Functions in SLE Patients

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    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.

  16. Neuromyelitis optica: Contribution of therapeutic responses markers monitoring in patients given rituximab.

    Science.gov (United States)

    Romero, G; Ticchioni, M; Cohen, M; Rosenthal-Allieri, M A; Mondot, L; Lebrun Frenay, C

    2016-03-01

    Neuromyelitis optica (NMO) is a central nervous system inflammatory autoimmune disease characterized by medullary and/or optical nerve damage. It is rare but life-threatening. Concerning the treatment of NMO, many drugs have been used in background therapy. Some studies have shown efficacy of rituximab (an antiCD20 monoclonal anti-body) either on the reduction of the annual number of exacerbation or the mean score EDSS. In 2013, a Korean team reported a new protocol during which they administered rituximab only when memory B lymphocytes CD27+ were detectable in the bloodstream. In our patient, institution of this protocol led to clinical benefit with a major decrease in the EDSS score over time (7 in August 2012 vs. 1 in October 2015), a reduction of the total administered dose (4g in 2013 vs. 1.375g in 2014 vs. 0g in 2015) and side effects. Compared with the rate of theoretical administration, health expenditure savings reached 1700 Euros per month over the 11-month treatment. Monitoring therapeutic response markers with memory B lymphocyte counts appear to be an efficient cost-effective way to measure clinical efficiency, reduce total doses, and limit side effects.

  17. Hindlimb-unloading suppresses B cell population in the bone marrow and peripheral circulation associated with OPN expression in circulating blood cells.

    Science.gov (United States)

    Ezura, Yoichi; Nagata, Junji; Nagao, Masashi; Hemmi, Hiroaki; Hayata, Tadayoshi; Rittling, Susan; Denhardt, David T; Noda, Masaki

    2015-01-01

    Rodent hindlimb unloading (HU) by tail-suspension is a model to investigate disuse-induced bone loss in vivo. Previously, we have shown that osteopontin (OPN, also known as Spp1) is required for unloading-induced bone loss. However, how unloading affects OPN expression in the body is not fully understood. Here, we examined OPN expression in peripheral blood of mice subjected to HU. Real-time RT-PCR analysis indicated that OPN expression is increased in circulating peripheral blood cells. This HU-induced increase in OPN mRNA expression was specific in circulating peripheral blood cells, as OPN was not increased in the blood cells in bone marrow. HU-induced enhancement in OPN expression in peripheral blood cells was associated with an increase in the fraction of monocyte/macrophage lineage cells in the peripheral blood. In contrast, HU decreased the fraction size of B-lymphocytes in the peripheral blood. We further examined if B-lymphogenesis is affected in the mice deficient for osteopontin subjected to HU. In bone marrow, HU decreased the population of the B-lymphocyte lineage cells significantly, whereas it did not alter the population of monocyte/macrophage lineage cells. HU also increased the cells in T-lymphocyte lineage in bone marrow. Interestingly, these changes were observed similarly both in OPN-deficient and wild-type mice. These results indicate for the first time that HU increases OPN expression in circulating cells and suppresses bone marrow B-lymphogenesis.

  18. Dengue Virus Directly Stimulates Polyclonal B Cell Activation

    Science.gov (United States)

    Papa, Michelle Premazzi; de Morais, Ana Theresa Silveira; Peçanha, Ligia Maria Torres; de Arruda, Luciana Barros

    2015-01-01

    Dengue infection is associated to vigorous inflammatory response, to a high frequency of activated B cells, and to increased levels of circulating cross-reactive antibodies. We investigated whether direct infection of B cells would promote activation by culturing primary human B lymphocytes from healthy donors with DENV in vitro. B cells were susceptible, but poorly permissive to infection. Even though, primary B cells cultured with DENV induced substantial IgM secretion, which is a hallmark of polyclonal B cell activation. Notably, DENV induced the activation of B cells obtained from either DENV immune or DENV naïve donors, suggesting that it was not dependent on DENV-specific secondary/memory response. B cell stimulation was dependent on activation of MAPK and CD81. B cells cultured with DENV also secreted IL-6 and presented increased expression of CD86 and HLA-DR, which might contribute to B lymphocyte co-stimulatory function. Indeed, PBMCs, but not isolated B cells, secreted high amounts of IgG upon DENV culture, suggesting that interaction with other cell types in vivo might promote Ig isotype switching and IgG secretion from different B cell clones. These findings suggest that activation signaling pathways triggered by DENV interaction with non-specific receptors on B cells might contribute to the exacerbated response observed in dengue patients. PMID:26656738

  19. Hematopoietic overexpression of FOG1 does not affect B-cells but reduces the number of circulating eosinophils.

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    Camille Du Roure

    Full Text Available We have identified expression of the gene encoding the transcriptional coactivator FOG-1 (Friend of GATA-1; Zfpm1, Zinc finger protein multitype 1 in B lymphocytes. We found that FOG-1 expression is directly or indirectly dependent on the B cell-specific coactivator OBF-1 and that it is modulated during B cell development: expression is observed in early but not in late stages of B cell development. To directly test in vivo the role of FOG-1 in B lymphocytes, we developed a novel embryonic stem cell recombination system. For this, we combined homologous recombination with the FLP recombinase activity to rapidly generate embryonic stem cell lines carrying a Cre-inducible transgene at the Rosa26 locus. Using this system, we successfully generated transgenic mice where FOG-1 is conditionally overexpressed in mature B-cells or in the entire hematopoietic system. While overexpression of FOG-1 in B cells did not significantly affect B cell development or function, we found that enforced expression of FOG-1 throughout all hematopoietic lineages led to a reduction in the number of circulating eosinophils, confirming and extending to mammals the known function of FOG-1 in this lineage.

  20. Novel potential ALL low-risk markers revealed by gene expression profiling with new high-throughput SSH-CCS-PCR.

    Science.gov (United States)

    Qiu, J; Gunaratne, P; Peterson, L E; Khurana, D; Walsham, N; Loulseged, H; Karni, R J; Roussel, E; Gibbs, R A; Margolin, J F; Gingras, M C

    2003-09-01

    The current systems of risk grouping in pediatric acute lymphoblastic leukemia (ALL) fail to predict therapeutic success in 10-35% of patients. To identify better predictive markers of clinical behavior in ALL, we have developed an integrated approach for gene expression profiling that couples suppression subtractive hybridization, concatenated cDNA sequencing, and reverse transcriptase real-time quantitative PCR. Using this approach, a total of 600 differentially expressed genes were identified between t(4;11) ALL and pre-B ALL with no determinant chromosomal translocation. The expression of 67 genes was analyzed in different cytogenetic ALL subgroups and B lymphocytes isolated from healthy donors. Three genes, BACH1, TP53BPL, and H2B/S, were consistently expressed as a significant cluster associated with the low-risk ALL subgroups. A total of 42 genes were differentially expressed in ALL vs normal B lymphocytes, with no specific association with any particular ALL subgroups. The remaining 22 genes were part of a specific expression profile associated with the hyperdiploid, t(12;21), or t(4;11) subgroups. Using an unsupervised hierarchical cluster analysis, the discriminating power of these specific expression profiles allowed the clustering of patients according to their subgroups. These genes could help to understand the difference in treatment response and become therapeutical targets to improve ALL clinical outcomes.