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Protection against Fas-dependent Thl-mediated apoptosis by antigen receptor engagement in B cells

Abstract

CYTOTOXIC CD4+ Thl-cells induce cell death by triggering a Fas-dependent apoptotic pathway1–6. Potential targets include activated B cells3,7, but it is not known whether the mode of B-cell stimulation influences susceptibility to Thl-mediated cytotoxicity. Here we report that CD40-Iigand-stimuIated B cells were extremely sensitive, whereas anti-IgM-stimulated B cells were resistant, to Fas-mediated apoptosis. B cells stimulated by both CD40L and anti-IgM were not susceptible to cytolysis, demonstrating that anti-IgM-mediated protection is an active, dominant process. Resistance to Thl-mediated cytotoxicity was similarly observed in CD40L-stimulated 3–83 (anti-H–2Kk,b)8 transgenic B cells co-cultured with H–2Kk or H–2Kb (but not H–2Kd) spleno-cytes. These results indicate that B cells can participate in regulating their own destruction. Protection against Fas-dependent apoptosis afforded by immunoglobulin–receptor engagement may constitute a fail-safe mechanism that eliminates bystander B cells activated by CD40L-expressing T cells, but ensures survival of antigen-specific B cells.

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Rothstein, T., Wang, J., Panka, D. et al. Protection against Fas-dependent Thl-mediated apoptosis by antigen receptor engagement in B cells. Nature 374, 163–165 (1995). https://doi.org/10.1038/374163a0

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