Phospholipase Cgamma2 provides survival signals via Bcl2 and A1 in different subpopulations of B cells.
PLCgamma2 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 PLCgamma2 deficiency specifically blocks B cell maturation at the transitional type 2 (T2) to follicular (FO) B cell transition and the PLCgamma2 pathway regulates survival of B cells. BCR-induced apoptosis is dramatically enhanced in all subsets of splenic PLCgamma2-deficient B cells, especially in T2 and FO B cell subpopulations. We also find that all splenic PLCgamma2-deficient B cell subpopulations express abnormally low levels of Bcl-2 protein. In addition, PLCgamma2 deficiency disrupts BCR-mediated induction of A1 expression. Enforced expression of Bcl-2 prevents BCR-induced apoptosis in all splenic PLCgamma2-deficient B cell subpopulations and partially restores the numbers of PLCgamma2-deficient FO B cells. In contrast to Bcl-2, enforced expression of A1 preferentially prevents BCR-induced apoptosis in PLCgamma2-deficient FO B cells and partially restores the numbers of these B cells. Therefore, the PLCgamma2 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.
Wen
Renren
R
Blood Research Institute, the Blood Center of Southeastern Wisconsin, Milwaukee, Wisconsin 53226, USA.
Chen
Yuhong
Y
Xue
Liquan
L
Schuman
James
J
Yang
Shoua
S
Morris
Stephan W
SW
Wang
Demin
D
D000818:Animals; D017209:Apoptosis; D001402:B-Lymphocytes / Q000378:metabolism; D015153:Blotting, Western; D016026:Bone Marrow Transplantation; D002469:Cell Separation; D002470:Cell Survival; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005434:Flow Cytometry; D006801:Humans; D020287:In Situ Nick-End Labeling; D051379:Mice; D051966:Phospholipase C gamma; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D051381:Rats; D051818:Replication Protein C; D012190:Retroviridae; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013154:Spleen / Q000378:metabolism; D013997:Time Factors; D010738:Type C Phospholipases / Q000378:metabolism*
D004268:DNA-Binding Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D010738:Type C Phospholipases; D051966:Phospholipase C gamma; D051818:Replication Protein C