Defective immunoglobulin class switching in Vav-deficient mice is attributable to compromised T cell help

A Gulbranson-Judge, V L Tybulewicz, A E Walters, K M Toellner, I C MacLennan, Martin Turner

Research output: Contribution to journalArticlepeer-review

40 Citations (Scopus)

Abstract

Vav, a guanine nucleotide exchange factor for members of the Rho family of small GTPases, is activated through engagement of B and T lymphocyte antigen receptors. It is important for establishing the signaling threshold of the TCR, as mice lacking Vav display defective thymocyte selection. Here, conventional B cells are shown to develop normally in Vav-deficient mice but these mice have few B-1 B cells. The threshold for inducing B cell proliferation through BCR engagement in vitro is greater in Vav-deficient B cells. Nevertheless, in vivo the mutant mice have normal antibody responses to haptenated Ficoll. In contrast, Vav-/- mice show defective class switching to IgG and germinal center formation when immunized with haptenated protein. Interestingly, this defect is reversed in chimeras where normal T cells are present. Antigen-specific proliferation of T cells in the T zone was found to be similar in wild-type and Vav-/- mice but the induction of IL-4 mRNA and switch transcripts was specifically impaired. These results suggest that defective immunoglobulin class switching in Vav-deficient mice is attributable to compromised T cell help.
Original languageEnglish
Pages (from-to)477-87
Number of pages11
JournalEuropean Journal of Immunology
Volume29
Issue number2
DOIs
Publication statusPublished - Feb 1999

Keywords

  • Lymphocyte Activation
  • Animals
  • Proto-Oncogene Proteins
  • Cell Cycle Proteins
  • Mice
  • Immunoglobulin Class Switching
  • Gene Expression Regulation
  • B-Lymphocytes
  • Lymphocyte Cooperation
  • T-Lymphocytes
  • Proto-Oncogene Proteins c-vav
  • Mice, Knockout

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