INHIBITION OF CASPASE ACTIVITY PREVENTS ANTI-IGM INDUCED APOPTOSIS BUT NOT CERAMIDE GENERATION IN WEHI-231 B-CELLS

In apoptosis induced by Reaper in Drosophila, as well as in a number o f other systems, it has been suggested that the increased synthesis of ceramide might be a consequence of the activation of the caspase/ICE (Interleukin-1 beta converting enzyme) protease pathway involved in ce ll death, implying that ceramide generation might often be the result rather than the cause of apoptosis. WEHI 231 B cells have previously b een shown to undergo apoptosis following exposure to exogenous ceramid e and to produce increased amounts of ceramide in response to anti-IgM crosslinking. We show here that in WEHI 231 cells a peptide inhibitor of caspase activity blocks cell death in response to both anti-IgM an d exogenous ceramide. However, the induction of ceramide synthesis by WEHI 231 cells in response to anti-IgM crosslinking is not blocked by this peptide. These results indicate that antigen receptor induced cer amide generation in WEHI 231 cells does not require caspase activation , and support the view that ceramide generation in immature B cells ma y be the cause rather than the consequence of activation of the caspas e dependent death pathway. (C) 1998 Elsevier Science Ltd. All rights r eserved.