The PI3K p110delta is required for down-regulation of RAG expression in immature B cells

J Immunol. 2007 Feb 15;178(4):1981-5. doi: 10.4049/jimmunol.178.4.1981.

Abstract

At the immature B cell stage the BCR signals the down-regulation of the RAG genes and Ig L chain (LC) allelic and isotype exclusion. The signaling pathway that regulates these events is poorly characterized. We demonstrate that immature B cells from mice deficient in the PI3K catalytic subunit p110delta fail to suppress RAG expression and inappropriately recombine kappa and lambda LC loci. In addition, in the presence of the autoantigen, clonal deletion and receptor editing still takes place, demonstrating that these processes are independent of p110delta. These results demonstrate a role for p110delta in the regulation of RAG gene expression and thereby LC allelic/isotype exclusion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoantigens / immunology
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism*
  • Class I Phosphatidylinositol 3-Kinases
  • Clonal Deletion / genetics
  • Clonal Deletion / immunology
  • DNA-Binding Proteins / biosynthesis*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / immunology
  • Down-Regulation / physiology*
  • Homeodomain Proteins / biosynthesis*
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / immunology
  • Immunoglobulin Class Switching / genetics
  • Immunoglobulin Class Switching / immunology
  • Immunoglobulin Light Chains / biosynthesis
  • Immunoglobulin Light Chains / genetics
  • Immunoglobulin Light Chains / immunology
  • Immunoglobulin kappa-Chains / biosynthesis
  • Immunoglobulin kappa-Chains / genetics
  • Immunoglobulin kappa-Chains / immunology
  • Mice
  • Mice, Knockout
  • Phosphatidylinositol 3-Kinases / deficiency
  • Phosphatidylinositol 3-Kinases / immunology
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Proto-Oncogene Proteins c-bcr / genetics
  • Proto-Oncogene Proteins c-bcr / immunology
  • Proto-Oncogene Proteins c-bcr / metabolism

Substances

  • Autoantigens
  • DNA-Binding Proteins
  • Homeodomain Proteins
  • Immunoglobulin Light Chains
  • Immunoglobulin kappa-Chains
  • Rag2 protein, mouse
  • RAG-1 protein
  • Class I Phosphatidylinositol 3-Kinases
  • Pik3cd protein, mouse
  • Bcr protein, mouse
  • Proto-Oncogene Proteins c-bcr