VpreB1/VpreB2/lambda 5 triple-deficient mice show impaired B cell development but functional allelic exclusion of the IgH locus

J Immunol. 2002 Jun 15;168(12):6286-93. doi: 10.4049/jimmunol.168.12.6286.

Abstract

At the precursor B cell stage during bone marrow B cell development, Ig muH chain associates with surrogate L (SL) chain, which is encoded by the three genes VpreB1, VpreB2, and lambda 5, to form the pre-B cell receptor (pre-BCR). Surface expression of the pre-BCR is believed to signal both proliferation and allelic exclusion of the IgH locus. Mice which lack either VpreB1/VpreB2 or lambda 5 show a lack of precursor B cell expansion but normal IgH allelic exclusion. This would suggest that one of either lambda 5 or VpreB can make a pre-BCR-like complex which is still able to signal allelic exclusion but not proliferation. To investigate this, we established mice lacking all components of the SL chain. These mice showed severely impaired B cell development which was similar to that previously found in mice lacking either lambda 5 or VpreB1/VpreB2. Surprisingly, the IgH locus was still allelically excluded and thus the SL chain appears not to be involved in allelic exclusion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles*
  • Animals
  • Antibody Formation / genetics
  • B-Lymphocyte Subsets / immunology
  • B-Lymphocyte Subsets / metabolism
  • B-Lymphocyte Subsets / pathology*
  • Bone Marrow Cells / immunology
  • Bone Marrow Cells / metabolism
  • Bone Marrow Cells / pathology
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology
  • Crosses, Genetic
  • Gene Expression Regulation / immunology
  • Genetic Markers / immunology
  • Hematopoietic Stem Cells / immunology
  • Hematopoietic Stem Cells / metabolism
  • Hematopoietic Stem Cells / pathology*
  • Immunoglobulin Heavy Chains / genetics*
  • Immunoglobulin Light Chains / biosynthesis
  • Immunoglobulin Light Chains / genetics*
  • Immunoglobulin Light Chains, Surrogate
  • Immunoglobulin M / blood
  • Lymphocyte Count
  • Lymphopenia / genetics*
  • Lymphopenia / immunology
  • Lymphopenia / pathology
  • Membrane Glycoproteins / biosynthesis
  • Membrane Glycoproteins / genetics*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Peritoneum / immunology
  • Peritoneum / pathology
  • Spleen / immunology
  • Spleen / pathology

Substances

  • Genetic Markers
  • Immunoglobulin Heavy Chains
  • Immunoglobulin Light Chains
  • Immunoglobulin Light Chains, Surrogate
  • Immunoglobulin M
  • Membrane Glycoproteins