Nature Immunology
2, 542 - 547 (2001)
doi:10.1038/88748
Signal transduction through Vav-2 participates in humoral immune responses and B cell maturationGina M. Doody1, 4, Sarah E. Bell1, Elena Vigorito1, Elizabeth Clayton1, Simon McAdam1, Reuben Tooze2, 5, Claire Fernandez1, Insong James Lee3, 6
& Martin Turner11
Laboratory of Lymphocyte Signaling and Development, Molecular Immunology Programme, The Babraham Institute, Babraham, Cambridge CB2 4AT, UK. 2
Department of Histopathology, Box 235, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2QQ, UK. 3
Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, MD 20906, USA. 4
Present address: Molecular Medicine Unit, University of Leeds, St. James's University Hospital, Leeds LS9 7TF, UK. 5
Present address: Department of Histopathology, Leeds General Infirmary, Great George Street, Leeds LS1 3EX, UK. 6
Present address: EpiGenesis Pharmaceuticals Inc., 2005 Eastpark Blvd, Cranbury, NJ 08512, USA.
Correspondence should be addressed to Martin Turner martin.turner@bbsrc.ac.ukB and T lymphocytes develop normally in mice lacking the guanine nucleotide exchange factor Vav-2. However, the immune responses to type II thymus-independent antigen as well as the primary response to thymus-dependent (TD) antigen are defective. Vav-2−deficient mice are also defective in their ability to switch immunoglobulin class, form germinal centers and generate secondary immune responses to TD antigens. Mice lacking both Vav-1 and Vav-2 contain reduced numbers of B lymphocytes and display a maturational block in the development of mature B cells. B cells from Vav-1-/-Vav-2-/- mice respond poorly to antigen receptor triggering, both in terms of proliferation and calcium release. These studies show the importance of Vav-2 in humoral immune responses and B cell maturation.
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