Phospholipase Cγ2 Provides Survival Signals via Bcl2 and A1 in Different Subpopulations of B Cells*

PLCγ2 plays a critical role in B cell receptor (BCR) signaling and its targeted deletion results in defective B cell development and function. Here, we show that PLCγ2 deficiency specifically blocks B cell maturation at the transitional type 2 (T2) to follicular (FO) B cell transition and the PLCγ2 pathway regulates survival of B cells. BCR-induced apoptosis is dramatically enhanced in all subsets of splenic PLCγ2-deficient B cells, especially in T2 and FO B cell subpopulations. We also find that all splenic PLCγ2-deficient B cell subpopulations express abnormally low levels of Bcl-2 protein. In addition, PLCγ2 deficiency disrupts BCR-mediated induction of A1 expression. Enforced expression of Bcl-2 prevents BCR-induced apoptosis in all splenic PLCγ2-deficient B cell subpopulations and partially restores the numbers of PLCγ2-deficient FO B cells. In contrast to Bcl-2, enforced expression of A1 preferentially prevents BCR-induced apoptosis in PLCγ2-deficient FO B cells and partially restores the numbers of these B cells. Therefore, the PLCγ2 pathway provides a survival signal via regulation of Bcl-2 in all splenic B cell subpopulations and via additional induction of A1 in mature FO B cells.