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Crosslinking of B- or T-cell antigen receptors results in the rapid tyrosine phosphorylation of a number of proteins, including Vav, a protein expressed in cells of the haematopoietic system. Vav contains an array of structural motifs that include Src-homology domains SH2/SH3 and regions of homology to the guanine-nucleotide-exchange protein Dbl, pleckstrin and protein kinase C (refs 5-9). Using the RAG-complementation approach, we have analysed in vivo differentiation and in vitro responses of B- and T-lineage cells generated by injection of embryonic stem cells homozygous for a null mutation in the vav gene into blastocysts of RAG-1- or RAG-2-deficient mice. Here we report that antigen receptor-mediated proliferative responses of B and T cells in vitro are severely reduced in the absence of Vav. We also suggest a direct link between the low proliferative response of Vav-deficient B and T cells and the reduced number of these cells in peripheral lymphoid organs of chimaeric mice.

Original publication

DOI

10.1038/374467a0

Type

Journal article

Journal

Nature

Publication Date

30/03/1995

Volume

374

Pages

467 - 470

Keywords

Animals, Antibody Formation, B-Lymphocytes, Cell Cycle Proteins, Cell Differentiation, Cell Division, Cell Line, Chimera, Mice, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-vav, Receptors, Antigen, Signal Transduction, T-Lymphocytes