CONCURRENT ENGAGEMENT OF CD40 AND THE ANTIGEN RECEPTOR PROTECTS NAIVEAND MEMORY HUMAN B-CELLS FROM APO-1 FAS-MEDIATED APOPTOSIS/

Naive and memory B cells were isolated from human tonsils and examined for expression of APO-1/Fas and for their sensitivity to the APO-1-de pendent apoptosis. APO-1 was found to be constitutively expressed on m emory but not on naive B cells. The susceptibility of both cell types to the APO-1 apoptotic pathway was acquired upon CD40 triggering and w as correlated with increased expression of the APO-1 receptor. Both na ive and memory B cells were protected from the APO-1-mediated death si gnal after dual ligation of the Ag receptor and CD40. Our findings sug gest that the APO-1 pathway controls the specificity of B cell respons es to T-dependent Ags and that occupancy of the Ag receptor dictates t he outcome of APO-1 ligation on B cell survival.