PLCγ2 regulates Bcl-2 levels and is required for survival rather than differentiation of marginal zone and follicular B cells

B cells from phospholipase C (PLC)gamma 2-deficient mice express reduced levels of the pro-survival protein Bcl-2 and show a defect in the development of transitional T3 and marginal zone (MZ) B cells that reflects reduced B cell survival. Introduction of a bcl-2 transgene restored the numbers of MZ, T3 and follicular B cells in PLC gamma 2(-/-) mice. Restricting the B cell repertoire in PLC gamma 2-deficient mice by the introduction of a BCR transgene resulted in a striking reduction in the number of IgM-positive B cells and a paucity of IgD-expressing cells in the spleen which was also rescued by the bcl-2 transgene. BCR-stimulated ERK and I kappa B alpha phosphorylation were PLC gamma 2 dependent, while calcium flux was reduced, but not abrogated, in the absence of PLC gamma 2, suggesting an ancillary role for PLC gamma 1. The bcl-2 transgene rescued development of PLC gamma 2(-/-) B cells and serum IgM levels but did not restore BCR-mediated signaling, proliferation or serum IgG3 levels. These data suggest that PLC gamma 2 performs a critical role in B cell development through regulation of survival rather than differentiation.