Defective immunoglobulin class switching in Vav-deficient mice is attributable to compromised T cell help
Research output: Contribution to journal › Article › peer-review
Vav, a guanine nucleotide exchange factor for members of the Rho family of small GTPases, is activated through engagement of B and T lymphocyte antigen receptors. It is important for establishing the signaling threshold of the TCR, as mice lacking Vav display defective thymocyte selection. Here, conventional B cells are shown to develop normally in Vav-deficient mice but these mice have few B-1 B cells. The threshold for inducing B cell proliferation through BCR engagement in vitro is greater in Vav-deficient B cells. Nevertheless, in vivo the mutant mice have normal antibody responses to haptenated Ficoll. In contrast, Vav-/- mice show defective class switching to IgG and germinal center formation when immunized with haptenated protein. Interestingly, this defect is reversed in chimeras where normal T cells are present. Antigen-specific proliferation of T cells in the T zone was found to be similar in wild-type and Vav-/- mice but the induction of IL-4 mRNA and switch transcripts was specifically impaired. These results suggest that defective immunoglobulin class switching in Vav-deficient mice is attributable to compromised T cell help.
|Number of pages||11|
|Journal||European Journal of Immunology|
|Publication status||Published - Feb 1999|
- Lymphocyte Activation, Animals, Proto-Oncogene Proteins, Cell Cycle Proteins, Mice, Immunoglobulin Class Switching, Gene Expression Regulation, B-Lymphocytes, Lymphocyte Cooperation, T-Lymphocytes, Proto-Oncogene Proteins c-vav, Mice, Knockout