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Targeted disruption of the MHC class II Aa gene in C57BL/6 mice.

The MHC class II gene Aa was disrupted by targeted mutation in embryonic stem (ES) cells derived from C57BL/6 mice to prevent expression of MHC class II molecules. Contrary to previous reports, the effect of the null-mutation on T cell development was investigated in C57BL/6 mice, which provide a defined genetic background. The complete lack of cell surface expression of MHC class II molecules in B6-Aa0/Aa0 homozygous mutant mice was directly demonstrated by cytofluorometric analysis using anti-Ab and anti-Ia specific mAbs. Development of CD4+CD8- T cells in the thymus was largely absent except for a small population of thymocytes expressing high levels of CD4 together with low amounts of CD8. The majority of these cells express the TCR at high density. Although mature CD4+CD8- T cells were undetectable in the thymus, some T cells with a CD4+CD8-TCRhigh phenotype were found in lymph nodes and spleen. Peripheral T cells from the mutant mice can be polyclonally activated in vitro with the mitogen concanavalin A. However, they could not be stimulated with staphylococcal enterotoxin B in autologous lymphocyte reactions, thereby demonstrating the absence of MHC class II expression in these mice. Peripheral B cells in B6-Aa0/Aa0 mutants were functional and responded to the T cell independent antigen levan by the production of antigen-specific IgM antibodies similar to wild-type cells. The B6-Aa0/Aa0 mutant mice described in this study represent an important tool to investigate the involvement of MHC class II molecules in lymphocyte maturation and the immune response.

Pubmed ID: 8398989

Authors

  • Köntgen F
  • Süss G
  • Stewart C
  • Steinmetz M
  • Bluethmann H

Journal

International immunology

Publication Data

August 28, 1993

Associated Grants

None

Mesh Terms

  • Animals
  • Antigens, CD4
  • Antigens, CD8
  • Antigens, T-Independent
  • Base Sequence
  • Female
  • Genes, MHC Class II
  • Histocompatibility Antigens Class II
  • Immunization
  • Mice
  • Mice, Inbred C57BL
  • Molecular Sequence Data
  • Mutation
  • Phenotype
  • Receptors, Antigen, T-Cell
  • T-Lymphocytes