Defective antigen receptor-mediated proliferation of B and T cells in the absence of Vav.
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.
Tarakhovsky
A
A
Institute for Genetics, University of Cologne, Germany.
Turner
M
M
Schaal
S
S
Mee
P J
PJ
Duddy
L P
LP
Rajewsky
K
K
Tybulewicz
V L
VL
D000818:Animals; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000166:cytology* / Q000378:metabolism; D018797:Cell Cycle Proteins; D002454:Cell Differentiation / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D002460:Cell Line; D002678:Chimera; D051379:Mice; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D051567:Proto-Oncogene Proteins c-vav; D011946:Receptors, Antigen / Q000378:metabolism*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology* / Q000378:metabolism
D018797:Cell Cycle Proteins; D011518:Proto-Oncogene Proteins; D051567:Proto-Oncogene Proteins c-vav; D011946:Receptors, Antigen; C496619:Vav1 protein, mouse