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Cutting Edge: The PI3K p110 Is Required for Down-Regulation of RAG Expression in Immature B Cells¹

Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Cambridge, United Kingdom

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 p110 fail to suppress RAG expression and inappropriately recombine and 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 p110. These results demonstrate a role for p110 in the regulation of RAG gene expression and thereby LC allelic/isotype exclusion.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by Medical Research Council and the Biotechnology and Biological Sciences Research Council.

² Address correspondence and reprint requests to Dr. Inga-Lill Mårtensson, Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, The Babraham Campus, Cambridge CB2 4AT, U.K. E-mail address: lill.martensson{at}bbsrc.ac.uk

³ Abbreviations used in this paper: HC, H chain; LC, L chain; TG, transgene; BM, bone marrow; LN, lymph node.

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