Activation sensitizes human memory B cells to B-cell receptor-induced apoptosis

The outcome of antigen receptor (B-cell receptor; BCR) ligation on B-cell s urvival can be influenced by multiple parameters. They are linked to the ph ysical properties of the antigen itself, the maturational stage of the cell s and the costimuli provided by different components of the innate and acqu ired immunity. Here we report that apoptosis prevails over stimulation when a BCR agonist is applied to human memory B cells which have been preactiva ted by CD40 ligand or anti-immunoglobulin antibodies. The susceptibility of activated memory B cells to BCR-induced killing is correlated with their e nhanced expression of the transcripts encoding the pro-apoptotic molecules Bar, c-Myc and p53. The BCR-mediated apoptosis of activated memory B cells does not require extensive cross-linking of the antigen receptors and relie s neither on engagement of the Fc gamma RII nor on the Fas/Fas ligand (Fas- L) system. Our findings suggest that activation stimuli open the BCR-induce d apoptotic pathway in memory B cells. Therefore we propose that the concep t of activation-induced cell death (AICD), originally described for T cells , also applies to mature B lymphocytes. The functions fulfilled by the AICD of mature B cells in the regulation of B-cell responses are discussed.