The CD40-ilnducible Bcl-2 family member A1 protects B cells from antigen receptor-mediated apoptosis

CD40 activation is necessary for thymus-dependent humoral immune responses and rescuing both phenotypically immature WEHI-231 B lymphoma cells from B cell antigen receptor-induced cell death and germinal center B cells from s pontaneous apoptosis. As some effects of CD40 are probably mediated by diff erences in gene expression, cDNA expression arrays and RNase protection ass ays were used to identify the anti-apoptotic Bcl-2 homolog A1 as a CD40-ind ucible gene in B cell lines and purified germinal center B cells. Sustained CD40-induced A1 upregulation correlated with CD40-mediated rescue of WEHI- 231 cells ii om anti-IgM-induced apoptosis. Moreover, overexpression of Al specifically protected WEHI-231 cells from anti-IgM-induced apoptosis but n ot cell death triggered by certain other stimuli. (C) 2000 Academic Press.