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Publication : Allelic 'choice' governs somatic hypermutation in vivo at the immunoglobulin kappa-chain locus.

First Author  Fraenkel S Year  2007
Journal  Nat Immunol Volume  8
Issue  7 Pages  715-22
PubMed ID  17546032 Mgi Jnum  J:123344
Mgi Id  MGI:3718137 Doi  10.1038/ni1476
Citation  Fraenkel S, et al. (2007) Allelic 'choice' governs somatic hypermutation in vivo at the immunoglobulin kappa-chain locus. Nat Immunol 8(7):715-22
abstractText  Monoallelic demethylation and rearrangement control allelic exclusion of the immunoglobulin kappa-chain locus (Igk locus) in B cells. Here, through the introduction of pre-rearranged Igk genes into their physiological position, the critical rearrangement step was bypassed, thereby generating mice producing B cells simultaneously expressing two different immunoglobulin-kappa light chains. Such 'double-expressing' B cells still underwent monoallelic demethylation at the Igk locus, and the demethylated allele was the 'preferred' substrate for somatic hypermutation in each cell. However, methylation itself did not directly inhibit the activation-induced cytidine-deaminase reaction in vitro. Thus, it seems that the epigenetic mechanisms that initially bring about monoallelic variable-(diversity)-joining rearrangement continue to be involved in the control of antibody diversity at later stages of B cell development.
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