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J Exp Med. 2009 Jan 16;206(1):153-67. doi: 10.1084/jem.20081202. Epub 2008 Dec 29.

A role for the IgH intronic enhancer E mu in enforcing allelic exclusion.

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  • 1Hunter College and Graduate Center of the City University of New York, New York, NY 10065, USA.

Abstract

The intronic enhancer (E mu) of the immunoglobulin heavy chain (IgH) locus is critical for V region gene assembly. To determine E mu's subsequent functions, we created an Igh allele with assembled V(H) gene but with E mu removed. In mice homozygous for this E mu-deficient allele, B cell development was normal and indistinguishable from that of mice with the same V(H) knockin and E mu intact. In mice heterozygous for the E mu-deficient allele, however, allelic exclusion was severely compromised. Surprisingly, this was not a result of reduced suppression of V-DJ assembly on the second allele. Rather, the striking breakdown in allelic exclusion took place at the pre-B to immature B cell transition. These findings reveal both an important role for E mu in influencing the fate of newly arising B cells and a second checkpoint for allelic exclusion.

PMID:
19114667
[PubMed - indexed for MEDLINE]
PMCID:
PMC2626684
Free PMC Article
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