Abstract
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.
Original language | English |
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Pages (from-to) | 477-87 |
Number of pages | 11 |
Journal | European Journal of Immunology |
Volume | 29 |
Issue number | 2 |
DOIs | |
Publication status | Published - Feb 1999 |
Keywords
- 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