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Query: UNIPROT:P10415 (Bcl-2)
 33,771 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent studies have established that interleukin (IL)-10 induces growth and most notably differentiation of normal human B lymphocytes. We studied here the effects of IL-10 on the proliferation and survival of B-chronic lymphocytic leukemia (B-CLL) cells. IL-10 was found to inhibit 54-96% of the spontaneous tritiated thymidine incorporation observed in 3 of 12 B-CLL samples. Furthermore, IL-10 decreased the viable cell recovery of all five B-CLL samples tested, irrespective of whether cells were spontaneously synthesizing DNA or not. After 1 wk, B-CLL populations cultured with IL-10 were lost while those cultured without IL-10 survived. Flow cytometric analysis, DNA gel electrophoresis, and Giemsa staining all revealed that IL-10 induced B-CLL cells to die from apoptosis. This IL-10-mediated apoptosis was dose dependent and specific as it could be inhibited by a neutralizing anti-IL-10 antibody. B-CLL cells undergoing apoptosis in response to IL-10 showed decreased Bcl-2 protein levels. Addition of IL-2, IL-4, interferon gamma, and anti-CD40 monoclonal antibody prevented the IL-10-mediated apoptosis of B-CLL cells. None of the malignant B cell populations obtained from eight non-Hodgkin's lymphomas and three hairy cell leukemias underwent apoptosis after IL-10 treatment, thus suggesting that the apoptotic effect of IL-10 is specific for B-CLL cells. Thus, IL-10 inhibits the DNA synthesis and most notably the survival of B-CLL cells, findings that call for considering IL-10 in the immunotherapy of chemoresistant B-CLL.
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PMID:Interleukin 10 induces apoptotic cell death of B-chronic lymphocytic leukemia cells. 827 Aug 86

Plasma cells represent the final stage of B lymphocyte differentiation. Most plasma cells in secondary lymphoid tissues live for a few days, whereas those in the lamina propria of mucosa and in bone marrow live for several weeks. To investigate the regulation of human plasma cell survival, plasma cells were isolated from tonsils according to high CD38 and low CD20 expression. Tonsillar plasma cells express CD9, CD19, CD24, CD37, CD40, CD74, and HLA-DR, but not CD10, HLA-DQ, CD28, CD56, and Fas/CD95. Although plasma cells express intracytoplasmic Bcl-2, they undergo swift apoptosis in vitro and do not respond to CD40 triggering. Bone marrow fibroblasts and rheumatoid synoviocytes, however, prevented plasma cells from undergoing apoptosis in a contact-dependent fashion. These data indicate that fibroblasts may form a microenvironment favorable for plasma cell survival under normal and pathological conditions.
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PMID:Bcl-2+ tonsillar plasma cells are rescued from apoptosis by bone marrow fibroblasts. 855 Dec 26

We have assessed during B cell development, the regulation and function of bcl-x, a member of the bcl-2 family of apoptosis regulatory genes. Here we show that Bcl-xL, a product of bcl-x, is expressed in pre-B cells but downregulated at the immature and mature stages of B cell development. Bcl-xL but not Bcl-2 is rapidly induced in peripheral B cells upon surface immunoglobulin M (IgM) cross-linking, CD40 signaling, or LPS stimulation. Transgenic mice that overexpressed Bcl-xL within the B cell lineage exhibited marked accumulation of peripheral B cells in lymphoid organs and enhanced survival of developing and mature B cells. B cell survival was further increased by simultaneous expression of bcl-xL and bcl-2 transgenes. These studies demonstrate that Bcl-2 and Bcl-xL are regulated differentially during B cell development and activation of mature B cells. Induction of Bcl-xL after signaling through surface IgM and CD40 appears to provide mature B cells with an additional protective mechanism against apoptotic signals associated with antigen-induced activation and proliferation.
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PMID:bcl-x exhibits regulated expression during B cell development and activation and modulates lymphocyte survival in transgenic mice. 862 51

The new and growing family of interleukin-1beta-converting enzyme (ICE) cysteine proteases are now recognised to be major effectors of cellular death by apoptosis. Like other members of this family, the CPP32/Yama proform is activated by processing to its active heterodimeric enzyme or apopain when it likely contributes to the process of apoptosis by cleaving poly(ADP-ribose) polymerase (PARP) and thereby inhibiting much of its DNA repair activity. Apoptosis plays a fundamental role in the regulation of the immune system where it is involved in the selection of both T and B lymphocytes bearing antigen receptor (AgR) for non-self. Cells of the Ramos Epstein-Barr virus (EBV)-genome-negative Burkitt lymphoma (BL) B cell line (Ramos-BL) can be triggered into growth arrest and apoptosis by treating with the calcium ionophore ionomycin or by crosslinking their surface AgR with antibodies directed against immunoglobulin (Ig)M (anti-IgM). Ionomycin- and AgR-triggered growth arrest and apoptosis are arrested by signals transduced through the surface CD40 of Ramos-BL B cells. Both ionomycin and anti-IgM trigger activation of CPP32 and cleavage of PARP prior to the onset of apoptosis; this process is abrogated by treatment with anti-CD40 and is independent of Bcl-2 expression. A tripeptide inhibitor of ICE family cysteine proteases, Z-Val-Ala-Asp-fluoromethylketone (zVAD-fmk) inhibits ionomycin- and AgR-triggered CPP32 activation, PARP cleavage and apoptosis, but not growth arrest, in Ramos-BL B cells. Thus, in this report we demonstrate that in a physiological system, activation of endogenous members of the ICE family, including CPP32, and cleavage of the death substrate PARP act as major effectors of apoptotic death.
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PMID:Ligation of CD40 rescues Ramos-Burkitt lymphoma B cells from calcium ionophore- and antigen receptor-triggered apoptosis by inhibiting activation of the cysteine protease CPP32/Yama and cleavage of its substrate PARP. 864 64

We have described recently the prevention of apoptosis by CD2-soluble CD48 interaction on antigen B cell receptor occupancy. Here, we show that CD2 ligation is also able to interfere with B cell receptor-independent apoptosis pathways such as spontaneous death in spleen B cells or serum deprivation and hydrogen peroxide exposure in the BAL-17 cell line. In all cases, CD2 ligation induces a signal that prevents the downregulation of Bcl-2 expression. The specific CD2 signal pathway involved in this phenomenon is still unknown. As reported, CD2 did not appear to induce Ca2+ mobilization, phosphatidylinositol turnover, or PKC translocation in B cells. Nevertheless, we show that CD2 receptor ligation is coupled to the tyrosine phosphorylation pathway in B cells. These observations indicate that CD2 is functionally able to trigger at least an early signal that could play a role in apoptosis blockage B cells in addition to the adhesion one. The results suggest the participation of cellular membrane receptors other that CD40 in apoptosis rescue, not only in the antigen-dependent but also in the antigen-independent phases of B cell lymphopoiesis.
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PMID:CD2 ligation abrogates antigen-independent apoptosis in B cells. 866 Aug 37

The authors recently reported that CD2 ligation rescues B cells from antigen-induced apoptosis by upregulation of intracellular Bcl-2 levels. However, the characterization of the early signals involved in apoptosis rescue by CD2 ligation has not been well established. In this context, CD2 does not promote either phosphatidylinositol turnover or CA2+ mobilization in B cells. In this paper the authors show that CD2 interaction with its ligand CD48 also reduces the apoptosis induced by forskolin and the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine and, to a much lesser extent, the apoptosis induced by cholera toxin in murine B splenocytes. Using a cAMP detection system sensitive to the picomolar range, the authors demonstrate that CD2-CD48 interaction decreases the intracellular cAMP concentrations induced by forskolin but not by cholera toxin. In comparison with the CD2-CD48 interaction, CD40-CD40 ligand interaction completely inhibits the apoptosis induced by cAMP increases without affecting the intracellular cAMP levels promoted by forskolin or cholera toxin. These results indicate that CD2 can also control the apoptosis at the very early steps after receptor signalling, such as the adenylate cyclase activity. Given that heterotrimeric G-proteins can mediate the adenylate cyclase activity the authors suggest that CD2 signalling could act through these small proteins, which would explain the inability of CD2 signalling to rescue from the apoptosis induced by cholera toxin, a Gs-protein activator. Conversely, CD40 seems to control apoptosis further downstream of the cAMP-PKA pathway where the survival and apoptotic signals are confluent, which might therefore render it a more efficient system to block apoptosis.
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PMID:Decrease in cAMP levels promoted by CD48-CD2 interaction correlates with inhibition of apoptosis in B cells. 866 20

Both rapid B-cell proliferation and programmed cell death (PCD) occur during the differentiation and selection of B cells within the germinal center. To help elucidate the role of Bcl-x in B-cell antigen selection and PCD within the germinal center, we examined its expression in defined B-cell populations and by immunochemistry of tonsil tissue. Purified B-cell fractions enriched for centrocytes express high amounts of Bcl-x and relatively low amounts of Bcl-2, whereas fractions enriched for centroblasts lack significant levels of both proteins. Consistent with this observation, immunocytochemistry localized Bcl-x within cells scattered throughout the germinal center. Stimulation of tonsil B cells with either CD40 or Staphylococcus aureus Cowan increase bcl-x mRNA and protein levels. Treatment of a cell line with a germinal center phenotype (RAMOS) or the tonsillar B-cell centroblast fraction with CD40 rapidly increased Bcl-x levels and partially rescued B cells from PCD. These data suggest that Bcl-x rather than Bcl-2 may rescue centrocytes during selection in the germinal center.
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PMID:Bcl-x rather than Bcl-2 mediates CD40-dependent centrocyte survival in the germinal center. 869 54

Using a Burkitt lymphoma cell line to model human B-cell apoptosis in vitro, we observed that crosslinking, by antibody, of cell surface immunoglobulin induced G1 growth-arrest followed by apoptosis. By contrast, cells treated with the Ca(2+)-ionophore, ionomycin, generated apoptotic signals in G2/M as well as in G1. Both ionomycin and anti-immunoglobulin treatment induced rapid dephosphorylation of Rb prior to apoptosis. Apoptosis was repressed following exposure to CD40-ligand and was accompanied by hyperphosphorylation of Rb and cell-cycle progression but not Bcl-2 expression. Expression of Bcl-2 protein in stable bcl-2-transfectants, also resulted in repression of apoptosis and anti-immunoglobulin-treated cells no longer underwent growth-arrest. In Bcl-2-expressing cells in which apoptosis was repressed, Rb remained hyperphosphorylated, even during G1-arrest induced by ionomycin. TGF beta treatment of Bcl-2-expressing cells induced G1-arrest, de-phosphorylation of Rb and apoptosis. These results suggest that the functional activity of Bcl-2 in B-lymphoma cells is dependent upon, or leads to, sustained hyperphosphorylation of Rb and that Rb hyperphosphorylation can be uncoupled from cell-cycle progression.
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PMID:Repression of apoptosis in human B-lymphoma cells by CD40-ligand and Bcl-2: relationship to the cell-cycle and role of the retinoblastoma protein. 871 Mar 76

CD95 (APO-1/Fas) is a member of the superfamily that includes the nerve growth factor and tumor necrosis factor receptors, OX40, CD27, CD30, and CD40. Present on a minority of resting blood lymphocytes, CD95 expression is upregulated on activated T and B lymphocytes and natural killer cells, where binding of the antigen by anti-Fas and anti-APO-1 antibodies has been shown to induce apoptosis. This CD95-mediated apoptosis is at least partially inhibited by expression of the Bcl-2 protooncogene. To evaluate possible roles of CD95 and Bcl-2 in growth regulation of lymphoid neoplasms, we studied by immunohistochemistry the expression of CD95 and Bcl-2 in 67 B- and 5 T-cell lymphomas, and 10 cases of Hodgkin's disease. In all, 29 B and 2 T cell lymphomas, and 9 cases of Hodgkin's disease expressed CD95. Compared with diffuse large B-cell and Burkitt-like lymphomas, lowgrade B-cell lymphomas more frequently expressed CD95 (52% versus 26%; P < .005). None of the B-cell small lymphocytic lymphomas or mantle cell lymphomas expressed CD95, whereas the majority of follicle center lymphomas, extranodal marginal zone B-cell lymphomas, and immunocytomas were CD95+. Of the 29 CD95+ B-cell lymphomas, only 33% of the high-grade group coexpressed Bcl-2, compared with 87% of the low-grade group (P < .04). Two of three peripheral T-cell lymphomas--including one anaplastic large cell lymphoma--expressed CD95. Staining for CD95 was seen in 9 of 10 cases of Hodgkin's disease. The infrequent expression of CD95 in high-grade B-cell lymphomas suggests an association between loss of CD95 expression/function and a more aggressive tumor grade. Whereas frequent coexpression of Bcl-2 with CD95 may protect low-grade B-cell lymphomas against CD95-mediated apoptosis, in the high-grade group such coexpression is infrequent, and other regulators besides Bcl-2 may be involved in modulating the apoptosis signal delivered by CD95.
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PMID:Expression of CD95 antigen and Bcl-2 protein in non-Hodgkin's lymphomas and Hodgkin's disease. 877 39

CD40--CD40L interactions between resting B cells and activated T cells are essential for germinal center formation. It has been shown that CD40L can induce both Fas expression and susceptibility to Fas-mediated killing in B cells, while anti-Ig can partially rescue B cells from Fas-mediated killing. However, the intracellular mechanism for this phenomenon is not known. We examined the expression of Fas and bcl-2 family gene products, such as Bcl-2, Bcl-x, Bax, and Mcl-1, in human tonsillar B cells. The activation of naive B cells by CD40L induced transient expression of Bcl-xL. As the Bcl-xL level decreased in CD40-activated B cells, the cells became susceptible to apoptosis by anti-Fas antibodies. Though anti-Ig did not change the Fas expression, it protected CD40-activated B cells from Fas-mediated killing by up-regulating Bcl-xL expression. The addition of anti-Ig did not significantly change Bcl-2, Bax, and Mcl-1 levels compared to those of B cells activated by CD40L alone.
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PMID:Up-regulation of Bcl-xL expression protects CD40-activated human B cells from Fas-mediated apoptosis. 887 10


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