Requirement of phospholipase C-γ2 activation in surface immunoglobulin M-induced B cell apoptosis

Abstract

Surface IgM (sIgM) stimulation induces the tyrosine phosphorylation of multiple cellular substrates, including phospholipase C (PLC)-γ2, which is involved in the activation of phosphatidylinositol pathway. DT40 B cells underwent apoptotic cell death when activated through sIgM, a phenomenon that is related to elimination of self-reactive B cells. To examine the roles of PLC-γ2 in sIgM signaling, we have generated DT40 cells deficient in PLC-γ2 Cross-linking of sIgM on PLC-γ2-deficient cells evoked neither inositol 1,4,5-trisphosphate nor calcium mobilization. In PLC-γ2- or Syk-deficient DT40 cells, the induction of apoptosis was blocked, but was still observed in Lyn-deficient cells. Src homology 2 domains of PLC-γ2 were essential for both its activation and sIgM-induced apoptosis. Since tyrosine phosphorylation of PLC-γ2 is mediated by Syk, these results indicate that activation of PLC-γ2 through Syk is required for sIgM-induced apoptosis.