title: PLCgamma2 regulates Bcl-2 levels and is required for survival rather than differentiation of marginal zone and follicular B cells.
abstract: 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.
authors.affiliation: Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Babraham, Cambridge CB2 4AT, GB. sarah-e.bell@bbsrc.ac.uk
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Bell
authors.forename: Elena
authors.initials: E
authors.lastname: Vigorito
authors.forename: Simon
authors.initials: S
authors.lastname: McAdam
authors.forename: Helen M
authors.initials: HM
authors.lastname: Reynolds
authors.forename: Anouk
authors.initials: A
authors.lastname: Caraux
authors.forename: Francesco
authors.initials: F
authors.lastname: Colucci
authors.forename: Martin
authors.initials: M
authors.lastname: Turner
mesh_terms: 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*
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; D011947:Receptors, Antigen, B-Cell; D010738:Type C Phospholipases; D051966:Phospholipase C gamma