DEFECTIVE ANTIGEN RECEPTOR-MEDIATED PROLIFERATION OF B-CELLS AND T-CELLS IN THE ABSENCE OF VAV

CROSSLINKING of B- or T-cell antigen receptors results in the rapid ty rosine phosphorylation of a number of proteins, including Vav, a prote in expressed in cells of the haematopoietic system contains an array o f structural motifs that include Src-homology domains SH2/SH3(4) and r egions of homology to the guanine-nucleotide-exchange nucleotide-excha nge protein Dbl, pleckstrin and protein kinase C (refs 5-9). Using the RAG-complementation approach(10), we have analysed in vivo differenti ation and in vitro responses of B- and T-lineage cells generated by in jection 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 r eport that antigen receptor-mediated proliferative responses of B and T cells in vitro are severely reduced in the absence of Vav. We also s uggest a direct link between the low proliferative response of Vav-def icient B and T cells and the reduced number of these cells in peripher al lymphoid organs of chimaeric mice.