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

THE product of the vav proto-oncogene¹, p95^vav or Vav, is tyrosine phosphorylated upon stimulation of T and B cells by antigen^2–4 and other^5–8 receptors, and contains motifs associated with signal transduction^{1, 9–11}To determine its role in vivo, we used t?at?-gene-targeted embryonic stem¹² cells and RAG-2^-/- blastocyst complementation¹³The 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 ligand^16–18Thus, we have established here a functional role for vav in the control of T-and B-cell development and activation.