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

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Abstract
B cells from phospholipase C (PLC)γ2‐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 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.