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Signal transduction through Vav-2 participates in humoral immune responses and B cell maturation

Abstract

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.

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Figure 1: Generation of Vav-2–deficient mice.
Figure 2: The response of Vav-2–deficient mice to TI antigen.
Figure 3: The response of Vav-2–deficient mice to TD antigen.
Figure 4: Reduced B cell numbers and altered ratio of IgM:IgD expression on B cells deficient in both Vav-1 and Vav-2.
Figure 5: Impaired BCR elicited a proliferative response in Vav-1−/− and Vav-1−/−Vav-2−/− mice.
Figure 6: Impaired BCR elicited Ca2+ response but normal tyrosine phosphorylation in Vav-2−/− and Vav-1−/−Vav2−/− mice

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Acknowledgements

We thank F. Flack, M. George and animal facility staff for technical assistance, G. Morgan for help with flow cytometry and D. Alexander, G. Butcher and L. Webb for a critical reading of the manuscript. Supported by Biotechnology and Biological Sciences Research Council Competitive Strategic Grant and the Leukaemia Research Fund and Cancer Research Campaign (to M. T.).

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Correspondence to Martin Turner.

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Doody, G., Bell, S., Vigorito, E. et al. Signal transduction through Vav-2 participates in humoral immune responses and B cell maturation. Nat Immunol 2, 542–547 (2001). https://doi.org/10.1038/88748

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