Defective antigen receptor-mediated proliferation of B and T cells in the absence of Vav

Nature. 1995 Mar 30;374(6521):467-70. doi: 10.1038/374467a0.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibody Formation
  • B-Lymphocytes / cytology*
  • B-Lymphocytes / metabolism
  • Cell Cycle Proteins*
  • Cell Differentiation / physiology
  • Cell Division / physiology
  • Cell Line
  • Chimera
  • Mice
  • Proto-Oncogene Proteins / physiology*
  • Proto-Oncogene Proteins c-vav
  • Receptors, Antigen / metabolism*
  • Signal Transduction
  • T-Lymphocytes / cytology*
  • T-Lymphocytes / metabolism

Substances

  • Cell Cycle Proteins
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-vav
  • Receptors, Antigen
  • Vav1 protein, mouse