Signal transduction through Vav-2 participates in humoral immune responses and B cell maturation.
B 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.
Doody
G M
GM
Laboratory of Lymphocyte Signaling and Development, Molecular Immunology Programme, The Babraham Institute, Babraham, Cambridge CB2 4AT, UK.
Bell
S E
SE
Vigorito
E
E
Clayton
E
E
McAdam
S
S
Tooze
R
R
Fernandez
C
C
Lee
I J
IJ
Turner
M
M
D000818:Animals; D000917:Antibody Formation; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D000955:Antigens, T-Independent / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology*; D018797:Cell Cycle Proteins; D002454:Cell Differentiation; D051379:Mice; D018345:Mice, Knockout; D015513:Oncogene Proteins / Q000235:genetics / Q000276:immunology*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000276:immunology; D051567:Proto-Oncogene Proteins c-vav; D015398:Signal Transduction
D000945:Antigens, Differentiation, T-Lymphocyte; D000955:Antigens, T-Independent; D018797:Cell Cycle Proteins; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; D051567:Proto-Oncogene Proteins c-vav; C496619:Vav1 protein, mouse; C490565:Vav2 protein, mouse