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Phospholipase Cgamma2 provides survival signals via Bcl2 and A1 in different subpopulations of B cells. J Biol Chem 2003 Oct 31;278(44):43654-62

Date

08/21/2003

Pubmed ID

12928432

DOI

10.1074/jbc.M307318200

Scopus ID

2-s2.0-0242321892   36 Citations

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.

Author List

Wen R, Chen Y, Xue L, Schuman J, Yang S, Morris SW, Wang D

Authors

Demin Wang PhD Assistant Professor in the Microbiology and Immunology department at Medical College of Wisconsin
Renren Wen PhD Associate Investigator in the Blood Research Institute department at BloodCenter of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Apoptosis
B-Lymphocytes
Blotting, Western
Bone Marrow Transplantation
Cell Separation
Cell Survival
Cells, Cultured
DNA-Binding Proteins
Flow Cytometry
Humans
In Situ Nick-End Labeling
Mice
Phospholipase C gamma
Proto-Oncogene Proteins c-bcl-2
Rats
Replication Protein C
Retroviridae
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction
Spleen
Time Factors
Type C Phospholipases
jenkins-FCD Prod-398 336d56a365602aa89dcc112f077233607d6a5abc