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The proto-oncogene product Vav is required for receptor clustering, proliferation, and differentiation of T cells, and Vav was identified as a substrate in the TCR and B cell receptor signaling pathway. The role of Vav in B cell responses to Ag challenge in vivo is not known. In this study, we show that Vav regulates B cell proliferation following in vitro activation of Ag receptors, but Vav has no apparent role in CD40-, IL-4-, or LPS-induced B cell activation. Increased degrees of Ag receptor cross-linking can partially reverse the proliferative defect in the anti-IgM response of vav-/- B cells. In vivo, vav-/- mice mounted protective antiviral IgM and IgG responses to infections with vesicular stomatitis virus and recombinant vaccinia virus expressing the vesicular stomatitis virus glycoprotein, which harbor repetitive surface epitopes that directly cross-link the Ag receptor and activate B cells in the absence of T cell help. vav-/- B cells also responded normally to the polyvalent, repetitive hapten Ag trinitrophenyl (TNP)-Ficoll that effectively cross-links B cell receptors. However, vav-/- mice failed to mount immune responses to the nonrepetitive, T cell-dependent hapten Ag (4-hydroxy-5-iodo-3-nitrophenyl)acetyl (NIP)-OVA. These results provide the first genetic evidence on the role of the guanine exchange factor Vav in immune responses to viral infections and antigenic challenge in vivo, and suggest that Vav adjusts the threshold for Ag receptor-mediated B cell activation depending on the nature of the Ag.

Type

Journal article

Journal

Journal of immunology (Baltimore, Md. : 1950)

Publication Date

07/1999

Volume

163

Pages

137 - 142

Addresses

Basel Institute for Immunology, Switzerland.

Keywords

B-Lymphocytes, Animals, Mice, Inbred C57BL, Mice, Knockout, Mice, Phenylacetates, Nitrophenols, Ovalbumin, Immunoglobulin M, Cell Cycle Proteins, Receptors, Antigen, B-Cell, Proto-Oncogene Proteins, Guanine Nucleotides, Antibodies, Viral, Antigens, Antigens, Viral, Haptens, Injections, Intravenous, Lymphocyte Activation, Proto-Oncogene Proteins c-vav, Vesicular stomatitis Indiana virus