PLCgamma2 regulates Bcl-2 levels and is required for survival rather than differentiation of marginal zone and follicular B cells.
B cells from phospholipase C (PLC)gamma2-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 PLCgamma2(-/-) mice. Restricting the B cell repertoire in PLCgamma2-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 IkappaBalpha phosphorylation were PLCgamma2 dependent, while calcium flux was reduced, but not abrogated, in the absence of PLCgamma2, suggesting an ancillary role for PLCgamma1. The bcl-2 transgene rescued development of PLCgamma2(-/-) B cells and serum IgM levels but did not restore BCR-mediated signaling, proliferation or serum IgG3 levels. These data suggest that PLCgamma2 performs a critical role in B cell development through regulation of survival rather than differentiation.
Bell
Sarah E
SE
Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Babraham, Cambridge CB2 4AT, GB. sarah-e.bell@bbsrc.ac.uk
Vigorito
Elena
E
McAdam
Simon
S
Reynolds
Helen M
HM
Caraux
Anouk
A
Colucci
Francesco
F
Turner
Martin
M
D000818:Animals; D016175:B-Lymphocyte Subsets / Q000378:metabolism; D001402:B-Lymphocytes / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology*; D002470:Cell Survival / Q000502:physiology; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D051379:Mice; D009154:Mutation; D051966:Phospholipase C gamma; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D010738:Type C Phospholipases / Q000235:genetics / Q000378:metabolism*
D019253:Proto-Oncogene Proteins c-bcl-2; D011947:Receptors, Antigen, B-Cell; D010738:Type C Phospholipases; D051966:Phospholipase C gamma