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

Abstract

B cells from phospholipase C (PLC)γ2-deficient mice express reduced levels of the prosurvival 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 PLCγ2-/- mice. Restricting the B cell repertoire in PLCγ2-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 IκBα phosphorylation were PLCγ2 dependent, while calcium flux was reduced, but not abrogated, in the absence of PLCγ2, suggesting an ancillary role for PLCγ1. The bcl-2 transgene rescued development of PLCγ2-/- B cells and serum IgM levels but did not restore BCR-mediated signaling, proliferation or serum IgG3 levels. These data suggest that PLCγ2 performs a critical role in B cell development through regulation of survival rather than differentiation. © 2004 Wiley-VCH Verlag GmbH & Co. KGaA.