Defective signalling through the T- and B-cell antigen receptors in lymphoid cells lacking the vav proto-oncogene

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Abstract
THE product of the vav proto-oncogene1, p95vav or Vav, is tyrosine phosphorylated upon stimulation of T and B cells by antigen2–4 and other5–8 receptors, and contains motifs associated with signal transduction1,9–11. To determine its role in vivo, we used t?at?-gene-targeted embryonic stem12 cells and RAG-2-/- blastocyst complementation13. The vav-/-–RAG-2-/- chimaeras displayed thymic atrophy with reduced numbers of peripheral T cells. Whereas the total number of B cells was normal, the subset of peritoneal B-l (CD5+)14 cells was missing. The vav-/- T and B cells were hyporeactive when stimulated through antigen receptors, but vav-/- T cells proliferated on exposure to phorbol ester and calcium ionophore15, whereas B cells responded normally to bacter-ial mitogen, lipopolysaccharide or the CD40 ligand16–18. Thus, we have established here a functional role for vav in the control of T-and B-cell development and activation.