Coupling Between B Cell Receptor and Phospholipase C-γ2 Is Essential for Mature B Cell Development

Two signaling pathways known to be essential for progression from immature to mature B cells are BAFF receptor (BAFF-R) and the B cell receptor (BCR). Here, we first show that phospholipase C (PLC)-γ2 is required for a BAFF-R–mediated survival signal. Then, we have examined the question of whether the reduced number of mature B cells in PLC-γ2(−/−) mice is caused by a defect in either BCR or BAFF-R signaling. We find that a PLC-γ2 SH2 mutant, which inhibits coupling between BCR and PLC-γ2, fails to restore B cell maturation, despite supporting BAFF-dependent survival. Therefore, our data suggest that the BAFF-R–mediated survival signal, provided by PLC-γ2, is not sufficient to promote B cell maturation, and that, in addition, activation of PLC-γ2 by BCR is required for B cell development.