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Avaliação do perfil dos linfócitos B de pacientes com Imunodeficiência Comun Variável antes a após administração de antígenos protéicos e polissacarídicos; Evaluation of B lymphocyte profile of Common Variable Immunodeficiency patients before and after immunization with protein and polysaccharide antigens

Baldassin, Maíra Pedreschi Marques
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Tese de Doutorado Formato: application/pdf
Publicado em 10/10/2014 PT
Relevância na Pesquisa
55.91%
Introdução: A Imunodeficiência Comum Variável (ICV) faz parte de um grupo de imunodeficiências primárias na qual os pacientes apresentam defeitos na maturação e diferenciação dos linfócitos B (LB), resultando em distúrbios funcionais além de alterações na distribuição de seus subtipos. Consequentemente, estes pacientes apresentam hipogamaglobulinemia, susceptibilidade a infecções e ausência de produção de anticorpos a antígenos específicos. Na tentativa de reduzir os episódios de infecções recorrentes, alguns trabalhos têm recomendado a vacinação com patógenos mortos ou subunidades e em trabalho anterior demonstramos a eficácia clínica da vacinação de pacientes com ICV, porém, a experiência com a administração de vacinas em imunocomprometidos é limitada. Objetivos: Avaliar a cinética da distribuição das subpopulações de linfócitos B antes e após a vacinação com antígenos proteicos e polissacarídicos em pacientes com ICV acompanhados no Ambulatório de Imunodeficiências Primárias do Hospital das Clínicas, FMUSP, além da produção de anticorpos específicos aos antígenos vacinais. Pacientes e Métodos: Um grupo de 35 pacientes com ICV e 16 controles foram vacinados contra Influenza...

Association between polyclonal B cell activation and the presence of autoantibodies in mice infected with Yersinia enterocolitica O:3

Medeiros, B. M M; Costa, A. M.; Araújo, P. M F; Falcão, D. P.
Fonte: Universidade Estadual Paulista Publicador: Universidade Estadual Paulista
Tipo: Artigo de Revista Científica Formato: 401-405
ENG
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Eight-week old conventional female Swiss mice were inoculated intravenously with Yersinia enterocolitica O:3. A second group of normal mice was used as control. Five mice from each group were bled by heart puncture and their spleens were removed for spleen cell collection on the 3rd, 5th, 7th, 10th, 14th and 21st day after infection. Immunoglobulin-secreting spleen cells were detected by the isotype-specific protein A plaque assay. Total immunoglobulin levels were determined in mouse serum by single radial immunodiffusion and the presence of autoantibodies was determined by ELISA. We observed a marked increase in the total number of cells secreting immunoglobulins of all isotypes as early as on the 3rd day post-infection and the peak of secretion occurred on the 7th day. At the peak of the immunoglobulin response, the total number of secreting cells was 19 times higher than that of control mice and most immunoglobulin-secreting cells were of the IgG2a isotype. On the 10th day post-infection, total serum immunoglobul in values were 2 times higher in infected animals when compared to the control group, and continued at this level up to the 21st day post-infection. Serum absorption with viable Y. enterocolitica cells had little effect on antibody levels detected by single radial immunodiffusion. Analysis of serum autoantibody levels revealed that Y. enterocolitica infection induced an increase of anti-myosin and anti-myelin immunoglobulins. The sera did not react with collagen. The present study demonstrates that Y. enterocolitica O:3 infection induces polyclonal activation of murine B cells which is correlated with the activation of some autoreactive lymphocyte clones.

Papel das proteínas Yops de Yersinia pseudotuberculosis na ativação dos linfócitos B

Medeiros, Beatriz Maria Machado; Souza, Cleide Dos Santos; Higuti, L.; Maia, Jose Mario Lourenco; Silva, Eloisa Elena Cangiani
Fonte: Universidade Estadual Paulista Publicador: Universidade Estadual Paulista
Tipo: Artigo de Revista Científica Formato: 53-60
POR
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Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq); Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP); The virulence plasmid common to pathogenic Yersinia species encodes a number of secreted proteins denoted Yops (Yersinia outer proteins). The Yops effectors have been related to a set of biological properties, including resistance to phagocytosis, cytotoxicity and dephosphorilation of host proteins. However, the interaction of Yops with the adaptive immune response is not clear. Yops secreted by Yersinia enterocolitica O:3 provoke policlonal activation of B lymphocyte, when inoculated in mice. In this work, Yops secreted by K pseudotuberculosis were inoculated by intravenous route in SPF Swiss mice, with the purpose of verify the in vivo role of these proteins in the splenic B lymphocyte activation. The kinetics of production of specific and nonspecific immunoglobulins of the different isotypes (IgG, IgA and IgM), was investigated by the technique of ELISPOT The presence of specific anu-Yersinia antibodies in the serum of the inoculated animals was also investigated by ELISA. It was observed a significant increase only in the number of nonspecific IgG-secreting lymphocytes, on the 21 st day after inoculation (a 2.5-fold increase compared to control). The number of lymphocytes secreting other isotypes of Ig was similar to the controls...

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

Alexandre-Moreira,M.S.; Piuvezam,M.R.; Pecanha,L.M.T.
Fonte: Associação Brasileira de Divulgação Científica Publicador: Associação Brasileira de Divulgação Científica
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/11/2003 EN
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55.9%
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...

Epstein-Barr virus nuclear proteins EBNA-3A and EBNA-3C are essential for B-lymphocyte growth transformation.

Tomkinson, B; Robertson, E; Kieff, E
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /04/1993 EN
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Recombinant Epstein-Barr viruses (EBV) with a translation termination codon mutation inserted into the nuclear protein 3A (EBNA-3A) or 3C (EBNA-3C) open reading frame were generated by second-site homologous recombination. These mutant viruses were used to infect primary B lymphocytes to assess the requirement of EBNA-3A or -3C for growth transformation. The frequency of obtaining transformants infected with a wild-type EBNA-3A recombinant EBV was 10 to 15%. In contrast, the frequency of obtaining transformants infected with a mutant EBNA-3A recombinant EBV was only 1.4% (9 mutants in 627 transformants analyzed). Transformants infected with mutant EBNA-3A recombinant virus could be obtained only by coinfection with another transformation-defective EBV which provided wild-type EBNA-3A in trans. Cells infected with mutant EBNA-3A recombinant virus lost the EBNA-3A mutation with expansion of the culture. The decreased frequency of recovery of the EBNA-3A mutation, the requirement for transformation-defective EBV coinfection, and the inability to maintain the EBNA-3A mutation indicate that EBNA-3A is essential or critical for lymphocyte growth transformation and that the EBNA-3A mutation has a partial dominant negative effect. Five transformants infected with mutant EBNA-3C recombinant virus EBV were also identified and expanded. All five also required wild-type EBNA-3C in trans. Serial passage of the mutant recombinant virus into primary B lymphocytes resulted in transformants only when wild-type EBNA-3C was provided in trans by coinfection with a transformation-defective EBV carrying a wild-type EBNA-3C gene. A secondary recombinant virus in which the mutated EBNA-3C gene was replaced by wild-type EBNA-3C was able to transform B lymphocytes. Thus...

The Epstein-Barr virus nuclear protein encoded by the leader of the EBNA RNAs is important in B-lymphocyte transformation.

Mannick, J B; Cohen, J I; Birkenbach, M; Marchini, A; Kieff, E
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /12/1991 EN
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These experiments evaluate the role of the Epstein-Barr virus (EBV) nuclear antigen leader protein (EBNA-LP) in B-lymphocyte growth transformation by using a recombinant EBV molecular genetic approach. Recombinant viruses encoding for a mutant EBNA-LP lacking the carboxy-terminal 45 amino acids were markedly impaired in their ability to transform primary B lymphocytes compared with EBNA-LP wild-type but otherwise isogenic recombinant viruses. This impairment was particularly evident when primary B lymphocytes were infected under conditions of limiting virus dilution. The impairment could be partially corrected by growth of the infected lymphocytes with fibroblast feeder layers or by cocultivation of primary B lymphocytes with relatively highly permissive mutant virus-infected cells. One of the five mutant recombinants recovered by growth of infected cells on fibroblast feeder cultures was a partial revertant which had a normal transforming phenotype. Several lymphoblastoid cell lines infected with the EBNA-LP mutant recombinant viruses had a high percentage of cells with bright cytoplasmic immunoglobulin staining, as is characteristic of cells undergoing plasmacytoid differentiation. Expression of the other EBV latent or lytic proteins and viral replication were not affected by the EBNA-LP mutations. Thus...

Demonstration of a B-lymphocyte mitogen produced by the Lyme disease pathogen, Borrelia burgdorferi.

Schoenfeld, R; Araneo, B; Ma, Y; Yang, L M; Weis, J J
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /02/1992 EN
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Lyme disease refers to the multisymptomatic illness in humans which results from infection with the tick-borne spirochete Borrelia burgdorferi. The white-footed mouse is the major reservoir for B. burgdorferi and, upon infection, certain inbred mice develop symptoms similar to those reported in human disease. Sonicated preparations of washed spirochetes were found to have potent mitogenic activity when cultured with lymphocytes from naive C57BL/6, C3H/HeJ, or BALB/c mice. The activity of the B. burgdorferi sonicate was approximately fourfold greater than that of a similarly prepared Escherichia coli sonicate. Polymyxin B efficiently inhibited the mitogenic activity of the E. coli sonicate but only slightly inhibited that of the B. burgdorferi sonicate, suggesting that a lipid A-containing lipopolysaccharide was not responsible for the B. burgdorferi activity. Kinetic analysis indicated peak proliferation at 2 to 3 days of culturing, suggesting polyclonal activation. B- and T-lymphocyte depletion experiments indicated that the major cell type responding to the B. burgdorferi mitogen was the B lymphocyte. This mitogen stimulated murine B cells not only to proliferate but also to differentiate into antibody-secreting cells, as demonstrated by the production of immunoglobulin by stimulated splenocytes. Furthermore...

B-lymphocyte responses to trinitrophenyl-conjugated Ficoll: requirement for T lymphocytes and Ia-bearing adherent cells.

Letvin, N L; Benacerraf, B; Germain, R N
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /08/1981 EN
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55.95%
These studies were done to characterize the cellular requirements for B-lymphocyte responses to the haptenated polysaccharide trinitrophenyl-conjugated Ficoll. By using an in vitro microculture system, it was demonstrated that hapten-specific anti-trinitrophenyl-conjugated Ficoll plaque-forming cell responses by B lymphocytes require Ia-bearing adherent accessory cells and Thy 1+ Lyt 1+2- nylon wool-nonadherent (T) lymphocytes. Such T cells could be primed in vivo with nonderivatized Ficoll to show carrier-specific helper cell function for derivatized Ficoll responses in vitro. The implications of these findings for our understanding of b-lymphocyte triggering by so-called T-independent antigens are discussed.

Specific human B lymphocyte alloantigens linked to HL-A.

Mann, D L; Abelson, L; Henkart, P; Harris, S D; Amos, D B
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /12/1975 EN
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Sera, previously found to react specifically with B lymphoid cultured cells, were tested on isolated T and B peripheral blood lymphocytes in a microcytotoxicity assay. Studies were performed on lymphocytes obtained from several large Amish families. The sera used in these studies were cytotoxic to peripheral blood, B lymphocytes, but not cytotoxic to T lymphocytes. The antigens detected followed the inheritance pattern of HL-A haplotypes. The strong linkage disequilibrium with HL-A antigens suggests that genes controlling the expression of B lymphocyte antigens are linked to genes controlling HL-A alloantigens.

The immunoglobulin heavy-chain B-lymphocyte enhancer efficiently stimulates transcription in non-lymphoid cells.

Wasylyk, C; Wasylyk, B
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /03/1986 EN
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55.93%
The mouse immunoglobulin heavy-chain (IgH) B-lymphocyte enhancer stimulates transcription from heterologous promoters 20- to 40-fold when transfected into several non-lymphoid cell lines. Stimulation in B-lymphocyte melanoma cell-lines is only about 5--10 times better. A central sequence is equally active in both cell types, whilst flanking sequences, on either side of the common enhancer sequences, specifically stimulate transcription in myeloma cells. These results suggest that there are factors in non-lymphoid cells that can interact with the IgH enhancer to stimulate transcription.

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

Han, T; Dadey, B
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /04/1978 EN
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55.98%
Human peripheral blood T and B lymphocytes were separated by a method based on the stable rosette formation of T lymphocytes with neuraminidase-treated sheep erythrocytes, followed by centrifugation over a Ficoll-Hypaque gradient. Monocytes were isolated from the T-depleted B lymphocyte preparation by allowing the monocytes to ingest iron particles and by subsequent centrifugation over a Ficoll-Hypaque gradient. The T lymphocytes responded extremely well to PHA and very well to PWM, while the B lymphocytes were unresponsive to either PHA or PWM. However, when the B lymphocytes were cultured together with irradiated autologous or allogeneic T lymphocytes (1:1, 1:2 or 1:4 ratio), both PHA and PWM became mitogenic to B lymphocytes. Irradiated T lymphocytes alone did not respond to either PHA or PWM, indicating that the 3H-thymidine incorporation seen in the mixed-cell culture was due to the activation of unirradiated B lymphocytes. The B lymphocytes failed to respond to these phytomitogens in the presence of lower concentrations of irradiated T lymphocytes. The monocytes were found to be incapable of helping the B lymphocytes to respond to PHA or PWM.

Multiple signaling pathways promote B lymphocyte stimulator–dependent B-cell growth and survival

Woodland, Robert T.; Fox, Casey J.; Schmidt, Madelyn R.; Hammerman, Peter S.; Opferman, Joseph T.; Korsmeyer, Stanley J.; Hilbert, David M.; Thompson, Craig B.
Fonte: American Society of Hematology Publicador: American Society of Hematology
Tipo: Artigo de Revista Científica
Publicado em 15/01/2008 EN
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We investigated the mechanism by which B lymphocyte stimulator (BLyS)/BAFF, a tumor necrosis factor superfamily ligand, promotes B-cell survival and resistance to atrophy. BLyS stimulation activates 2 independent signaling pathways, Akt/mTOR and Pim 2, associated with cell growth and survival. BLyS blocks the cell volume loss (atrophy) that freshly isolated B cells normally undergo when maintained in vitro while concurrently increasing glycolytic activity and overall metabolism. This atrophy resistance requires Akt/mTOR. We used a genetic approach to resolve the contributions of Akt/mTOR and Pim kinase pathways to BLyS-mediated survival. Pim 2–deficient B cells are readily protected from death by BLyS stimulation, but this protection is completely abrogated by treatment with the mTOR inhibitor rapamycin. Furthermore, rapamycin treatment in vivo significantly reduces both follicular and marginal zone B cells in Pim-deficient but not healthy hosts. BLyS-dependent survival requires the antiapoptotic protein Mcl-1. Mcl-1 protein levels rise and fall in response to BLyS addition and withdrawal, respectively, and conditional deletion of the Mcl-1 gene renders B cells refractory to BLyS-mediated protection. Because BlyS is required for the normal homeostasis of all B cells...

2,3,7,8-Tetrachlorodibenzo-p-dioxin–Mediated Suppression of Toll-Like Receptor Stimulated B-Lymphocyte Activation and Initiation of Plasmacytic Differentiation

North, Colin M.; Crawford, Robert B.; Lu, Haitian; Kaminski, Norbert E.
Fonte: Oxford University Press Publicador: Oxford University Press
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
55.89%
2,3,7,8-Tetrachlordibenzo-p-dioxin (TCDD) is a potent suppressor of humoral immunity, disrupting antibody production in response to both T cell–dependent and T cell–independent antigens. Among the cell types required for humoral responses, the B cell is highly, and directly, sensitive to TCDD. B cells become antibody-secreting cells via plasmacytic differentiation, a process regulated by several transcription factors, including activator protein-1, B-cell CLL/lymphoma 6 (BCL-6), and B lymphocyte–induced maturation protein 1 (Blimp-1). The overarching conceptual framework guiding experimentation is that TCDD disrupts plasmacytic differentiation by altering the expression or activity for upstream regulators of Blimp-1. Multiparametric flow cytometry was used to investigate TCDD-induced alterations in both activation marker and transcription factor expression following lipopolysaccharide (LPS) activation of purified B cells. TCDD significantly impaired LPS-activated expression of major histocompatibility complex class II, cluster of differentiation (CD)69, CD80, and CD86. Immunosuppressive concentrations of TCDD also suppressed LPS-activated Blimp-1 and phosphorylated c-Jun expression, whereas elevating BCL-6 expression. Because BCL-6 and c-Jun are directly and indirectly regulated by the kinases AKT...

The Essential role of cyclooxygenase-2 in B lymphocyte function : implications for antibody production and viral infection

Bernard, Matthew P. ; Phipps, Richard P.
Fonte: Universidade de Rochester Publicador: Universidade de Rochester
Tipo: Tese de Doutorado
ENG
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Thesis (Ph. D.)--University of Rochester. School of Medicine & Dentistry. Dept. of Microbiology & Immunology, 2009.; Generation of protective humoral immune responses against vaccines and pathogens depends on optimal B lymphocyte production of high-affinity antibodies. Non-steroidal anti-inflammatory drugs (NSAIDs) are used to curb undesirable symptoms of vaccination and infection, including pain, fever and swelling. However, relatively little is known about how these drugs may influence humoral immunity. NSAIDs function by inhibiting cyclooxygenase-1 (Cox-1), the constitutively expressed isoform and Cox-2, the inducible isoform. Our lab has previously shown that Cox-2 can be induced in response to T-dependent stimuli and that Cox-2 activity is important for B cell antibody production. However, no mechanism for the attenuated antibody production in the presence of Cox-2 selective inhibitors has been described. I hypothesized that: (i) T-independent stimuli, such as CpG DNA, induce Cox-2 in human B cells, (ii) CpG-induced antibody production is dependent on Cox-2 activity, (iii) Cox-2 activity is essential for B cell differentiation to antibody secreting plasma cells and (iv) Cox-2 activity is necessary for the optimal in vivo generation of neutralizing antibodies to live virus infection. Results presented herein...

Arrested B Lymphopoiesis and Persistence of Activated B Cells in Adult Interleukin 7

Carvalho, Thiago L.; Mota-Santos, Tomaz; Cumano, Ana; Demengeot, Jocelyne; Paulo, Vieira
Fonte: Fundação Calouste Gulbenkian Publicador: Fundação Calouste Gulbenkian
Tipo: Artigo de Revista Científica
Publicado em 15/10/2001
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55.98%
Interleukin 7 is a crucial factor for the development of murine T and B lymphocytes. We now report that, in the absence of interleukin 7, B lymphocyte production takes place exclusively during fetal and perinatal life, ceasing after 7 wk of age. In peripheral organs, however, the pool of B lymphocytes is stable throughout adult life and consists only of cells that belong to the B1 and marginal zone (MZ) compartments. This is accompanied by a 50-fold increase in the frequency of immunoglobulin (Ig)M- and IgG-secreting cells, and the concentration of serum immunoglobulins is increased three- to fivefold. Both the MZ phenotype and the increase in serum IgM are T cell independent. These findings reveal a previously undescribed pathway of B lymphopoiesis that is active in early life and is interleukin 7 independent. This pathway generates B1 cells and a normal sized MZ B lymphocyte compartment.

Polymorphism in the 5 ' regulatory region of the B-lymphocyte activating factor gene is associated with the Ro/La autoantibody response and serum BAFF levels in primary Sjogren's syndrome

Nossent, J.; Lester, S.; Zahra, D.; Mackay, C.; Rischmueller, M.
Fonte: Oxford Univ Press Publicador: Oxford Univ Press
Tipo: Artigo de Revista Científica
Publicado em //2008 EN
Relevância na Pesquisa
65.91%
Objective. To investigate the association between haplotypes in the 5' regulatory region of the B-lymphocyte activating factor (BAFF) gene, disease susceptibility and serum BAFF (s-BAFF) levels in Caucasian primary SS (pSS) patients. Methods. Case–control study in an established pSS cohort with PCR–RFLP genotyping for four SNPs (-2841 TC, -2704 TC, -2701 TA, -871 CT), which tag a haplotype block in the 5' regulatory region of the BAFF gene and s-BAFF determination by ELISA. Results. s-BAFF levels were elevated in Ro/La-positive pSS patients (n = 85, 1770 pg/ml) compared with both Ro/La-negative pSS patients (n = 27, 1193 pg/ml) and controls (n = 59, 1171 pg/ml), P < 0.001. s-BAFF increased with diversification of the anti-Ro/La antibody response, but was not correlated with age, RF or immunoglobulin G levels. There were four common BAFF haplotypes. While the CTAT haplotype was associated with Ro/La-positive pSS [odds ratio (OR) 2.6; 95% CI 1.7, 4.1; P = 0.00004], the TTTT haplotype was associated with elevated s-BAFF in autoantibody-positive pSS (n = 85; 88% females; P = 0.008). The shared -871 T allele had no independent contribution to disease susceptibility or s-BAFF. Conclusions. Disease susceptibility for Ro/La-positive pSS is increased with the CTAT haplotype...

Étude du dysfonctionnement du compartiment des cellules B chez des patients à différents stades d’infection par le virus d’immunodéficience humaine (VIH)

Valcke, Han Sang
Fonte: Université de Montréal Publicador: Université de Montréal
Tipo: Thèse ou Mémoire numérique / Electronic Thesis or Dissertation
FR
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56.05%
Les anomalies phénotypiques et fonctionnelles des lymphocytes B (LB) sont typiques d'une infection au VIH et se traduisent principalement par une activation polyclonale, une perte de la mémoire immunitaire ainsi qu'une réponse humorale déficiente et des phénomènes auto-immunitaires souvent précurseurs de lymphomes B. Ces anomalies se retrouvent principalement chez les patients lors de la phase chronique de la maladie et semblent être reliées en partie au niveau de la charge virale ainsi qu'à un compartiment de lymphocytes T CD4+ altéré. Cependant, quoique controversé, des éléments d’activation polyclonale ont également été observés chez les non-progresseurs à long terme (LTNPs) qui présentent une charge virale faible et un compartiment T CD4+ semblable aux individus séronégatifs. Ainsi, les objectifs principaux de cette étude sont 1) d’établir une chronologie des anomalies du compartiment des cellules B chez des individus infectés par le VIH qui ont une progression différente de la maladie (PHI normaux, rapides, sains et LTNP). 2) corréler les niveaux sériques du stimulateur de lymphocytes B (BLyS), un facteur de croissance des cellules B, avec les phénotypes observés chez ces mêmes patients. L’hyperglobulinémie...

Segregation of B Lymphocytes into Stationary Apoptotic and Migratory Proliferating Subpopulations in Agglomerate Cultures with Ileal Epithelium

Alitheen, N; McClure, Susan J; McCullagh, Peter
Fonte: Wiley-VCH Verlag GMBH Publicador: Wiley-VCH Verlag GMBH
Tipo: Artigo de Revista Científica
Relevância na Pesquisa
56%
The B lymphocyte-epithelial cell interactions that define the microenvironment of the ileal Peyer's patch, the primary B lymphocyte organ of the fetal lamb, have been replicated in tissue culture. Mixed suspensions of ileal epithelial cells, lymphocytes a

Role of Syk in B-cell development and antigen-receptor signaling

Cornall, Richard J; Cheng, Alex; Pawson, Tony; Goodnow, Christopher
Fonte: National Academy of Sciences (USA) Publicador: National Academy of Sciences (USA)
Tipo: Artigo de Revista Científica
Relevância na Pesquisa
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Antigen receptors (BCRs) on developing B lymphocytes play two opposing roles-promoting survival of cells that may later bind a foreign antigen and inhibiting survival of cells that bind too strongly to self-antigens. It is not known how these opposing outcomes are signaled by BCRs on immature B cells. Here we analyze the effect of a null mutation in the Syk tyrosine kinase on maturing B cells displaying a transgene-encoded BCR that binds hen egg lysozyme (HEL). In the absence of HEL antigen, HEL-specific BCRs are expressed normally on the surface: of Syk-deficient immature B-lineage cells, but this fails to promote maturation beyond the earliest stages of B-lineage commitment. Binding of HEL antigen, nevertheless, triggers phosphorylation of CD79α/β BCR subunits and modulation of receptors from the surface in Syk- deficient cells, but it cannot induce an intracellular calcium response. Continuous binding of low- or high-avidity forms of HEL, expressed as self- antigens, fails to restore the signal needed for maturation. Compared with the effects in the same system of null mutations in other BCR signaling elements, such as CD45 and Lyn kinase, these results indicate that Syk is essential for transmitting a signal that initiates the program of B- lymphocyte maturation.

A novel mechanism for complement activation at the surface of B cells following antigen binding

Manderson, A; Quah, Ben; Botto, Marina; Goodnow, Christopher; Walport, Mark J; Parish, Christopher
Fonte: American Association of Immunologists Publicador: American Association of Immunologists
Tipo: Artigo de Revista Científica
Relevância na Pesquisa
56.02%
Coligation of CD21 with BCR on the surface of B cells provides a costimulatory signal essential for efficient Ab responses to T-dependent Ags. To achieve this, Ag must be directly linked to C3 fragments, but bow this occurs in vivo is not fully understood. Using BCR transgenic mice, we demonstrated that C3 was deposited on the surface of B cells following both high- and moderate-affinity Ag binding. This was dependent on the specific binding of IgM to the BCR-bound Ag and can occur independently of soluble immune complex formation. Based on these data, we propose a novel model in which immune complexes can form directly on the surface of the B cell following Ag binding. This model has implications for our understanding of B lymphocyte activation.