B2, B1 and Marginal-Zone B-cell-subsets are distinguished by their location, phenotype and function. These subsets produce protective and autoreactive-Abs, then the fine-tuned-regulation of B-cell survival through apoptosis is critical to maintain humoral-immune-homeostasis. Our aim was to evaluate the susceptibility of B-cell-subsets to apoptosis induced by Fas and FcγRIIb (FcR). Phenotypic analysis of sorted B-cell-subsets from C57BL/6 mice showed that peritoneal B1-cells expressed higher levels of FcR and lower levels of Fas than peritoneal-B2 (pB2) and spleen-B-cells (sB). Evaluation of FcR and Fas expression after 48h-culture with CpG showed that TLR9-triggering upregulates both FcR and Fas in pB2 and sB. Activated B1-cells increased FcR but not Fas expression. Accordingly, pB2 and sB were susceptible to apoptosis via FcR and Fas, while B1-cells were susceptible only to FcR-induced apoptosis. Interestingly, BAFF, a cytokine critical for B-cells development, significantly diminished the expression of FcR in all the activated B-cell-subsets, reducing the susceptibility to FcR-induced-death. BAFF modified neither Fas expression nor Fas-mediated apoptosis. So, B-cell-subsets are regulated through different death-receptors, B2-cells are controlled by Fas and FcR while B1-cells are controlled only by FcR. We demonstrate that BAFF protect B-cells from FcR-mediated-apoptosis, highlighting a new mechanism through which BAFF favors B-cells survival and autoimmunity.
