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PMID:12928432
Citation |
Wen, R, Chen, Y, Xue, L, Schuman, J, Yang, S, Morris, SW and Wang, D (2003) Phospholipase Cgamma2 provides survival signals via Bcl2 and A1 in different subpopulations of B cells. J. Biol. Chem. 278:43654-62 |
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Abstract |
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. |
Links |
PubMed Online version:10.1074/jbc.M307318200 |
Keywords |
Animals; Apoptosis; B-Lymphocytes/metabolism; Blotting, Western; Bone Marrow Transplantation; Cell Separation; Cell Survival; Cells, Cultured; DNA-Binding Proteins/metabolism; Flow Cytometry; Humans; In Situ Nick-End Labeling; Mice; Phospholipase C gamma; Proto-Oncogene Proteins c-bcl-2/metabolism; Rats; Replication Protein C; Retroviridae; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction; Spleen/metabolism; Time Factors; Type C Phospholipases/metabolism |
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Significance
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Gene product | Qualifier | GO ID | GO term name | Evidence Code | with/from | Aspect | Notes | Status |
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