Differential regulation of B cell subsets survival by death-receptors and BAFF

AMEZCUA VESELY, MARIA CAROLINA; ACOSTA RODRIGUEZ, EVA V; BERMEJO, DANIELA A; MONTES, CAROLINA LUCIA; GRUPPI, ADRIANA

Vina del Mar, Chile

Congreso; 9th Latin American Congress of Immunology; 2009

Asociacion Latinoamericana de Inmunologia (ALAI)

Within the B cells, B2, B1 and Marginal Zone B cell subsets are distinguished by their location, phenotype and Ag specificity. These subsets produce protective Abs important during infection and also autoreactive Abs involved in autoimmunity. The fine-tuned regulation of B cell survival through apoptosis is a critical process to maintain humoral immune homeostasis. Our aim was to evaluate the susceptibility of different B cell subsets to the apoptosis induced by crosslinking of the death receptors, Fas and FcgRIIb (FcR). Phenotypic analysis of sorted B cell subsets from C57BL/6 miceshowed that peritoneal B1 cells expressed higher levels of FcR and lower levels of Fas than peritoneal B2 (pB2) and spleen B (sB) cells. Evaluation of FcR and Fas expression after 48h-culture with CpG (2 ug/ml) showed that TLR9 triggering upregulated both FcR and Fas in pB2 and sB. In contrast, activated B1 cells increased FcR but not Fas expression. Accordingly, pB2 and sB were susceptible to apoptosis via FcR as well as Fas crosslinking while B1 cells were susceptible to FcR-induced apoptosis but resistant to Fas-mediated cell death. We next addressed if receptor-mediated apoptosis of B cell subsets could be regulated by BAFF (B cell activating factor), a cytokine critical for survival, activation and maturation of B cells. Interestingly, BAFF (150 ng/ml) significantly diminished the expression of FcR in all the activated B cell subsets and, consequently, reduced the susceptibility of these cells to FcR-induced death. BAFF did modify neither Fas expression nor Fas-mediated apoptosis susceptibility. Our results show that survival of B cell subsets is regulated through different death receptors, B2 cells are controlled by Fas and FcR pathways while B1 cells are controlled only via FcR. In addition, we demonstrate that BAFF protect B cells from FcR mediated apoptosis, highlighting a new mechanism through which BAFF favors B cells survival and potentially contributes to autoimmunity.