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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.

Type

Journal article

Journal

J Immunol

Publication Date

15/02/2007

Volume

178

Pages

1981 - 1985

Keywords

Animals, Autoantigens, B-Lymphocytes, Clonal Deletion, DNA-Binding Proteins, Down-Regulation, Homeodomain Proteins, Immunoglobulin Class Switching, Immunoglobulin Light Chains, Immunoglobulin kappa-Chains, Mice, Mice, Knockout, Phosphatidylinositol 3-Kinases, Proto-Oncogene Proteins c-bcr