Defective signalling through the T- and B-cell antigen receptors in lymphoid cells lacking the vav proto-oncogene.
The product of the vav proto-oncogene, p95vav or Vav, is tyrosine phosphorylated upon stimulation of T and B cells by antigen and other receptors, and contains motifs associated with signal transduction. To determine its role in vivo, we used vav-gene-targeted embryonic stem cells and RAG-2-/- blastocyst complementation. 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-1 (CD5+) 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 ionophore, whereas B cells responded normally to bacterial mitogen, lipopolysaccharide or the CD40 ligand. Thus, we have established here a functional role for vav in the control of T- and B-cell development and activation.
Zhang
R
R
Division of Hematology/Oncology, Children's Hospital, Boston, Massachusetts 02115, USA.
Alt
F W
FW
Davidson
L
L
Orkin
S H
SH
Swat
W
W
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis; D001402:B-Lymphocytes / Q000166:cytology* / Q000378:metabolism; D018797:Cell Cycle Proteins; D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D002678:Chimera; D004268:DNA-Binding Proteins; D037181:Lectins, C-Type; D051379:Mice; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D051567:Proto-Oncogene Proteins c-vav; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology* / Q000378:metabolism; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D037181:Lectins, C-Type; D011506:Proteins; D011518:Proto-Oncogene Proteins; D051567:Proto-Oncogene Proteins c-vav; D011947:Receptors, Antigen, B-Cell; D011948:Receptors, Antigen, T-Cell; D000099192:CD69 Antigens; C499308:Rag2 protein, mouse; C064655:V(D)J recombination activating protein 2; C496619:Vav1 protein, mouse