scholarly journals Antibodies to HLA Class I α1 Domain Trigger Apoptosis of CD40-Activated Human B Lymphocytes

Blood ◽  
1997 ◽  
Vol 90 (2) ◽  
pp. 726-735 ◽  
Author(s):  
Laurent Genestier ◽  
Geneviève Meffre ◽  
Pierre Garrone ◽  
Jean-Jacques Pin ◽  
Yong-Jun Liu ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
B Lymphocytes ◽  
Apoptotic Cell ◽  
Interleukin 2 ◽  
Hla Class I ◽  
Class I ◽  
Activated T Cells ◽  
Hla Class I Molecules ◽  
Activated B Cells

We analyzed herein whether antibodies to HLA class I α1 domain, which trigger apoptosis of activated T cells, may also control the growth/survival of human B lymphocytes. Addition of monoclonal antibody (MoAb) 90 (mouse IgG1) or YTH862 (rat IgG2b) was found to strongly inhibit the proliferation of CD40-activated total tonsil B cells as well as that of purified naive, germinal center, and memory B-cell subsets. This inhibitory effect was not prevented by addition of B-cell tropic factors, such as interleukin-2 (IL-2), IL-4, and IL-10, and was a result of induced B-cell apoptosis as shown by using a TUNEL assay and DNA electrophoresis. In contrast, engagement of another epitope of the α1 domain, as well as that of the α2 and α3 domains by specific anti-HLA class I MoAbs, failed to inhibit DNA synthesis and to induce apoptosis of CD40-activated B cells. As recently reported for acquisition of sensitivity to Fas (APO-1/CD95) -dependent apoptosis, susceptibility to MoAb90-and YTH862-induced death was restricted to CD40-activated B cells, because resting and anti–IgM-activated B cells did not undergo apoptosis after HLA class I engagement. Moreover, ligation of the B-cell receptor protected CD40-activated B cells from both HLA class I- and Fas-mediated growth inhibition and apoptosis. Taken together, these results show that engagement of the α1 domain of HLA class I induces apoptotic cell death of CD40-activated, but not of antigen-activated B cells, and would, therefore, suggest a possible role for HLA class I molecules in the control of B-cell homeostasis.

scholarly journals Antibodies to HLA Class I α1 Domain Trigger Apoptosis of CD40-Activated Human B Lymphocytes

Blood ◽  
1997 ◽  
Vol 90 (2) ◽  
pp. 726-735 ◽  
Author(s):  
Laurent Genestier ◽  
Geneviève Meffre ◽  
Pierre Garrone ◽  
Jean-Jacques Pin ◽  
Yong-Jun Liu ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
B Lymphocytes ◽  
Apoptotic Cell ◽  
Interleukin 2 ◽  
Hla Class I ◽  
Class I ◽  
Activated T Cells ◽  
Hla Class I Molecules ◽  
Activated B Cells

Abstract We analyzed herein whether antibodies to HLA class I α1 domain, which trigger apoptosis of activated T cells, may also control the growth/survival of human B lymphocytes. Addition of monoclonal antibody (MoAb) 90 (mouse IgG1) or YTH862 (rat IgG2b) was found to strongly inhibit the proliferation of CD40-activated total tonsil B cells as well as that of purified naive, germinal center, and memory B-cell subsets. This inhibitory effect was not prevented by addition of B-cell tropic factors, such as interleukin-2 (IL-2), IL-4, and IL-10, and was a result of induced B-cell apoptosis as shown by using a TUNEL assay and DNA electrophoresis. In contrast, engagement of another epitope of the α1 domain, as well as that of the α2 and α3 domains by specific anti-HLA class I MoAbs, failed to inhibit DNA synthesis and to induce apoptosis of CD40-activated B cells. As recently reported for acquisition of sensitivity to Fas (APO-1/CD95) -dependent apoptosis, susceptibility to MoAb90-and YTH862-induced death was restricted to CD40-activated B cells, because resting and anti–IgM-activated B cells did not undergo apoptosis after HLA class I engagement. Moreover, ligation of the B-cell receptor protected CD40-activated B cells from both HLA class I- and Fas-mediated growth inhibition and apoptosis. Taken together, these results show that engagement of the α1 domain of HLA class I induces apoptotic cell death of CD40-activated, but not of antigen-activated B cells, and would, therefore, suggest a possible role for HLA class I molecules in the control of B-cell homeostasis.

scholarly journals Fas ligation induces apoptosis of CD40-activated human B lymphocytes.

1995 ◽  
Vol 182 (5) ◽  
pp. 1265-1273 ◽  
Author(s):  
P Garrone ◽  
E M Neidhardt ◽  
E Garcia ◽  
L Galibert ◽  
C van Kooten ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
B Lymphocytes ◽  
Cell Clone ◽  
Apoptotic Cell ◽  
Gradient Centrifugation ◽  
Cd40 Ligand ◽  
Activated T Cells ◽  
And Function

Since CD40/CD40 ligand (CD40Lig) interactions are essential in vivo for the generation of germinal center B cells that express Fas (Apo-1/CD95), we explored whether CD40 engagement may modulate Fas expression and function on human B lymphocytes. Resting tonsil B cells, isolated by density gradient centrifugation, express either absent or low levels of Fas. They could be induced to promptly express Fas after ligation of their CD40, however, using either a recombinant human CD40Lig or a cross-linked anti-CD40 mAb. In contrast, engagement of the B cell antigen receptor by immobilized anti-kappa and -lambda antibodies did not turn on Fas expression. Addition of anti-Fas mAb CH11 inhibited the later phases of CD40-induced B cell growth as a result of apoptotic cell death. Furthermore, Fas ligation inhibited proliferation and Ig secretion of CD40-activated B cells in response to recombinant cytokines such as interleukin (IL)-2, IL-4, and IL-10, as well as a cytokine-rich supernatant of phytohemagglutinin-activated T cells, indicating that none of those B cell tropic factors were able to prevent the Fas-induced death. Taken together, the present results show that engagement of CD40 antigen on B cells induces Fas expression and sensitizes them to Fas-mediated apoptosis. The delayed functional response to Fas ligation after CD40 activation may represent a way to limit the size of a specific B cell clone that is generated during T-B cell interactions.

scholarly journals Detection and functional studies of p60-65 (Tac antigen) on activated human B cells.

1984 ◽  
Vol 160 (5) ◽  
pp. 1597-1602 ◽  
Author(s):  
L K Jung ◽  
T Hara ◽  
S M Fu
Keyword(s):  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Cell Activation ◽  
Interleukin 2 ◽  
Receptor Expression ◽  
Pokeweed Mitogen ◽  
Activated T Cells ◽  
Human B Cells ◽  
Activated B Cells

A monoclonal antibody, AT-1, is shown to precipitate a p60-65 molecule identical to the Tac antigen. With AT-1, the expression of IL-2 receptors by normal activated human B cells from peripheral blood and tonsils is documented by biosynthetic and immunofluorescence studies. AT-1 precipitated a p60-65 protein from [35S]methionine-labeled activated B cells, similar to that from activated T cells. The interleukin 2 (IL-2) receptor appeared shortly after activation with anti-IgM and B cell-stimulatory factor(s). Its expression reached its peak at 60-72 h with approximately 50% of the B blasts stained by AT-1. Other modes of activation of B cells, by T cell-independent, formalin-treated staphylococci and Epstein-Barr virus, and by T cell-dependent pokeweed mitogen, also induced IL-2 receptor expression. The functional significance of this finding was investigated using recombinant IL-2 (rIL-2). While rIL-2 did not induce resting B cells to proliferate in the presence of anti-IgM, it induced activated B cells to proliferate in the absence of other factors. On the other hand, rIL-2 did not induce the differentiation of these activated B lymphocytes. These data suggest that IL-2 may play a significant role in B cell activation.

scholarly journals Fas-Independent Apoptosis of Activated T Cells Induced by Antibodies to the HLA Class I α1 Domain

Blood ◽  
1997 ◽  
Vol 90 (9) ◽  
pp. 3629-3639 ◽  
Author(s):  
Laurent Genestier ◽  
Romain Paillot ◽  
Nathalie Bonnefoy-Berard ◽  
Geneviéve Meffre ◽  
Monique Flacher ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
T Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
Heavy Chain ◽  
Hla Class I ◽  
Class I ◽  
T Cell Proliferation ◽  
Activated T Cells ◽  
Hla Class I Molecules

Abstract In addition to their major function in antigen presentation and natural killer cell activity regulation, HLA class I molecules may modulate T-cell activation and proliferation. Monoclonal antibodies (MoAbs) that recognize distinct epitopes of HLA class I molecules were reported to interfere with T-cell proliferation. We show here that two MoAbs (mouse MoAb90 and rat YTH862) that bind to an epitope of the α1 domain of HLA class I heavy chain induce apoptotic cell death of activated, but not resting, peripheral T lymphocytes. Other reference anti-HLA class I antibodies specific for distinct epitopes of the α1 (B9.12.1), α2 (W6/32), or α3 (TP25.99) domains of the heavy chain decreased T-cell proliferation but had little or no apoptotic effect. Apoptosis shown by DNA fragmentation, phosphatidylserine externalization, and decrease of mitochondrial transmembrane potential was observed whatever the type of T-cell activator. Apoptosis did not result from Fas/Fas-L interaction and distinct though partly overlapping populations of activated T cells were susceptible to Fas– and HLA class I–mediated apoptosis, respectively. Induction of apoptosis did not require HLA class I cross-linking inasmuch as it could be observed with monovalent Fab′ fragments. The data indicate that MoAb90 and YTH862 directed against the α1 domain of HLA class I trigger apoptosis of activated T lymphocytes by a pathway which does not involve Fas-ligand.

scholarly journals Selective inhibition of growth factor-dependent human B cell proliferation by monoclonal antibody AB1 to an antigen expressed by activated B cells.

1984 ◽  
Vol 160 (6) ◽  
pp. 1919-1924 ◽  
Author(s):  
L K Jung ◽  
S M Fu
Keyword(s):  
Monoclonal Antibody ◽  
Cell Proliferation ◽  
T Cells ◽  
B Cells ◽  
B Cell ◽  
Leukemic Cells ◽  
Activated T Cells ◽  
Igm Antibodies ◽  
Stimulatory Factor ◽  
Activated B Cells

A monoclonal antibody, AB1, was established with activated human B cells as immunogen. AB1 stained activated B cells but not activated T cells. Its selective reactivity to activated B cells was further documented by its nonreactivity to activated T cells, resting T and B cells, monocytes, granulocytes, bone marrow cells, leukemic cells, and cells from cell lines of T, B, and myeloid lineages. Upon activation, the antigen appeared on B cells as early as 3-4 h after stimulation and was fully expressed by 38 h. The expression of this antigen was not dependent on the presence of B cell stimulatory factor(s). Anti-IgM antibodies by themselves induced its expression. AB1 inhibited B cell proliferation that was induced by a low dose anti-IgM antibody and conditioned medium containing B cell stimulatory factor. It did not inhibit B cell proliferation induced by either high doses of anti-IgM antibodies or by formalinized Staphylococcus aureus. It also failed to inhibit T cell mitogenesis. The possibility exists that this antigen is related to the receptor for B cell stimulatory factor.

scholarly journals Interleukin 2 induces antigen-reactive T cell lines to secrete BCGF-I.

1983 ◽  
Vol 158 (6) ◽  
pp. 2024-2039 ◽  
Author(s):  
M Howard ◽  
L Matis ◽  
T R Malek ◽  
E Shevach ◽  
W Kell ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Cell Line ◽  
Cell Lines ◽  
Interleukin 2 ◽  
Activated T Lymphocytes ◽  
T Cell Lines ◽  
Activated B Cells

Antigen-activated T lymphocytes produce within 24 h of stimulation a factor that is indistinguishable biochemically and functionally from the B cell co-stimulating growth factor, BCGF-I, originally identified in induced EL4 supernatants: Supernatants from antigen-stimulated T cell lines are not directly mitogenic for resting B cells, but synergize in an H-2-unrestricted manner with anti-Ig activated B cells to produce polyclonal proliferation but not antibody-forming-cell development; biochemical studies reveal the B cell co-stimulating factor present in antigen-stimulated T cell line supernatants is identical by phenyl Sepharose chromatography and isoelectric focusing (IEF) to EL4 supernatant BCGF-I. We thus conclude that normal T cells produce BCGF-I in response to antigenic stimulation. Analysis of the mechanism of BCGF-I production by antigen-stimulated T cells showed that optimum amounts of BCGF-I were obtained as quickly as 24 h post-stimulation, and that the factor producing cells in the T cell line investigated bore the Lyt-1+2- phenotype. As few as 10(4) T cells produced sufficient BCGF-I to support the proliferation of 5 X 10(4) purified anti-Ig activated B cells. Finally, the activation of normal T cell lines to produce BCGF-I required either antigen presented in the context of syngeneic antigen-presenting cells (APC) or interleukin 2 (IL-2).

E47, IRF-4, and PU.1 synergize to induce B-cell-specific activation of the class II transactivator promoter III (CIITA-PIII)

Blood ◽  
2004 ◽  
Vol 104 (9) ◽  
pp. 2849-2857 ◽  
Author(s):  
Nienke van der Stoep ◽  
Edwin Quinten ◽  
Marisa Marcondes Rezende ◽  
Peter J. van den Elsen
Keyword(s):  
T Cells ◽  
B Cells ◽  
B Cell ◽  
B Lymphocytes ◽  
Regulatory Elements ◽  
Strong Reduction ◽  
Activated T Cells ◽  
Class Ii Transactivator ◽  
Human T Cells ◽  
E Box

Abstract In B cells, expression of CIITA and resulting major histocompatibility complex II (MHCII) is mediated exclusively by promoter III (CIITA-PIII) activation. Recent studies have established that CIITA-PIII also participates in the expression of CIITA in activated human T cells, dendritic cells, and monocytes. In this study we characterized the various regulatory elements and interacting factors of CIITA-PIII that account for specific activation in B lymphocytes. We identified 2 E-box motifs and an Ets/ISRE-consensus element (EICE) in CIITA-PIII as playing a crucial role in the B-cell-specific transcriptional regulation of CIITA. Abolishment of factor binding to these elements resulted in a strong reduction of CIITA-PIII activation in B cells only, whereas it did scarcely affect or not affect the activity of CIITA-PIII in activated T cells and monocytes. We show that in B cells, E47 and PU.1/IRF-4 interact with the E-box motifs and the EICE, respectively, and act synergistically in the activation of CIITA-PIII. Moreover, functional inhibition of either E47 or IRF-4 resulted in strong reduction of CIITA-PIII activity in B lymphocytes only. The finding that PU.1, IRF-4, and E47 play an important role in the B-cell-mediated activation of CIITA-PIII provides a link between antigen presentation functions and activation and differentiation events in B lymphocytes.

scholarly journals CELL INTERACTIONS IN THE IMMUNE RESPONSE IN VITRO

1972 ◽  
Vol 136 (4) ◽  
pp. 737-760 ◽  
Author(s):  
Marc Feldmann
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
B Lymphocytes ◽  
Cell Interaction ◽  
T And B Lymphocytes ◽  
Activated T Cells ◽  
Cell Cooperation

The mechanism of interaction of T and B lymphocytes was investigated in an in vitro hapten carrier system using culture chambers with two compartments separated by a cell impermeable nucleopore membrane. Because specific cell interaction occurred efficiently across this membrane, contact of T and B lymphocytes was not essential for cooperation which must have been mediated by a subcellular component or "factor." By using different lymphoid cell populations in the lower culture chamber and activated thymus cells in the upper chamber (with antigen present in both), it was found that the antigen-specific mediator acted indirectly on B cells, through the agency of macrophages. Macrophages which had been cultured in the presence of activated T cells and antigen acquired the capacity to specifically induce antibody responses in B cell-containing lymphoid populations. Trypsinization of these macrophages inhibited their capacity to induce immune responses, indicating that the mediator of cell cooperation is membrane bound. By using antisera to both the haptenic and carrier determinants of the antigen as blocking reagents, it was demonstrated that the whole antigen molecule was present on the surface of macrophages which had been exposed to activated T cells and antigen. Because specifically activated T cells were essential a component of the antigen-specific mediator must be derived from these cells. By using anti-immunoglobulin sera as inhibitors of the binding of the mediator to macrophages, the T cell component was indeed found to contain both κ- and µ-chains and was thus presumably a T cell-derived immunoglobulin. It was proposed that cell cooperation is mediated by complexes of T cell IgM and antigen, bound to the surface of macrophage-like cells, forming a lattice of appropriately spaced antigenic determinants. B cells become immunized by interacting with this surface. With this mechanism of cell cooperation, the actual pattern of antigen-B cell receptor interactions in immunization would be the same with both thymus-dependent and independent antigens. An essential feature of the proposed mechanism of cell cooperation is that macrophage-B cell interaction must occur at an early stage of the antibody response, a concept which is supported by many lines of evidence. Furthermore this mechanism of cell interaction can be elaborated to explain certain phenomena such as the highly immunogenic macrophage-bound antigen, antigenic competition, the distinction between immunity and tolerance in B lymphocytes, and the possible mediation of tolerance by T lymphocytes.

scholarly journals Recombinant interleukin 2 or 5, but not 3 or 4, induces maturation of resting mouse B lymphocytes and propagates proliferation of activated B cell blasts.

1988 ◽  
Vol 167 (4) ◽  
pp. 1377-1390 ◽  
Author(s):  
H Karasuyama ◽  
A Rolink ◽  
F Melchers
Keyword(s):  
B Cells ◽  
B Cell ◽  
Cell Line ◽  
Cell Cycle Progression ◽  
Interleukin 2 ◽  
Mitotic Cell ◽  
Beta Activity ◽  
Specific Antibodies ◽  
B Cell Signaling ◽  
Activated B Cells

Plasmacytoma transformants of the X63-Ag8-653 cell line carrying an expression vector with either IL-2, -3, -4, or -5 cDNA were established that secrete the corresponding ILs at high rates. The four mouse ILs (mILs) were then tested as single ILs and in combinations for their effects on the maturation of resting and proliferation of activated normal mouse splenic B cells. mIL-3 and mIL-4 were inactive in all assays. mIL-2, as well as mIL-5, synergized with Ig-specific antibodies and B cell growth factor alpha (BCGF-alpha) to stimulate successive rounds of B cell division with LPS-activated B cells. This activity as BCGF-beta was effective at concentrations similar to those at which mIL-2 induced proliferation of the CTL-L T cell line, indicating a high-affinity interaction of both mIL-2 and mIL-5 with their corresponding receptors on activated B cells. mIL-5 and maybe IL-2 also induced maturation of resting B cells to Ig-secreting cells without proliferation. This B cell maturation factor (BMF) activity of mIL-5 was as effective as its BCGF-beta activity, while the BMF activity of mIL-2 was at least 10(2)-fold less effective. BMF activity of mIL-2, but not mIL-5, was blocked by anti-Il-2-R antibodies, indicating that mIL-2 and mIL-5 use separate receptors for B cell signaling. mIL-2, as well as mIL-5, furthermore, acted as filler activities when proliferation in the presence of Ig-specific antibodies and BCGF-alpha was measured with as little as 500 B cells. In the case of mIL-5, this was also true for maturation of that few cells. Limiting dilution analyses showed that approximately 1-2% of the resting B cells matured without division, while 30-100-fold fewer cells (0.03-0.06%) proliferated and matured in response to IL-5. A single IL, therefore, is capable of inducing maturation and of stimulating mitotic cell cycle progression of normal B cells.

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