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Publication : A role for nuclear factor kappa B/rel transcription factors in the regulation of the recombinase activator genes.

First Author  Verkoczy L Year  2005
Journal  Immunity Volume  22
Issue  4 Pages  519-31
PubMed ID  15845455 Mgi Jnum  J:97978
Mgi Id  MGI:3576839 Doi  10.1016/j.immuni.2005.03.006
Citation  Verkoczy L, et al. (2005) A role for nuclear factor kappa b/rel transcription factors in the regulation of the recombinase activator genes. Immunity 22(4):519-31
abstractText  In developing B cells, expression of surface immunoglobulin is an important signal to terminate recombinase activator gene (RAG) expression and V(D)J recombination. However, autoreactive antigen receptors instead promote continued gene rearrangement and receptor editing. The regulation by B cell receptor (BCR) signaling of RAG expression and editing is poorly understood. We report that in editing-competent cells BCR ligand-induced RAG mRNA expression is regulated at the level of RAG transcription, rather than mRNA stability. In immature B cells carrying innocuous receptors, RAG expression appears to be under rapidly reversible negative regulation. Studies involving transduction of a superrepressive (sr) I kappa B alpha protein indicate that NF-kappaB/Rel proteins promote RAG transcription. Interestingly, NF kappa B1-deficient cells overexpress RAG and undergo an exaggerated receptor editing response. Our data implicate NF kappa B transcription factors in the BCR-mediated regulation of RAG locus transcription. Rapidly activated NF kappa B pathways may facilitate prompt antigen receptor-regulated changes in RAG expression important for editing and haplotype exclusion.
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