Requirement o f Phospholipase C - ~ , 2 Activation in Surface Immunog lobu l in M - induced B Cell Apoptosis

Surface IgM (slgM) stimulation induces the tyrosine phosphorylation of multiple cellular substrates, including phospholipase C (PLC)-'~/2, which is involved in the activation ofphosphatidyhnositol pathway. DT40 B cells underwent apoptotic cell death when activated through slgM, a phenomenon that is related to elimination of self-reactive B cells. To examine the roles of PLC-~/2 in slgM signaling, we have generated DT40 cells deficient in PLC-y2 Cross-linking ofslgM on PLC-y2-deficient cells evoked neither inositol 1,4,5-trisphosphate nor calcium mobilization. In PLC-T2or Syk-deficient DT40 cells, the induction of apoptosis was blocked, but was still observed in Lyn-deficient cells. Src homology 2 domains of PLC-T2 were essential for both its activation and slgM-induced apoptosis. Since tyrosine phosphorylation of PLC-T2 is mediated by Syk, these results indicate that activation of PLC-T2 through Syk is required for slgM-induced apoptosis.