The Journal of Experimental Medicine
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Published online December 29, 2008
doi:10.1084/jem.20081202
The Journal of Experimental Medicine
The Rockefeller University Press, 0022-1007 $30.00
© 2008 Li et al.
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ARTICLE

 A role for the IgH intronic enhancer Eµ in enforcing allelic exclusion

Fubin Li and Laurel A. Eckhardt

Hunter College and Graduate Center of the City University of New York, New York, NY 10065

CORRESPONDENCE Laurel A. Eckhardt: eckhardt{at}genectr.hunter.cuny.edu

The intronic enhancer (Eµ) of the immunoglobulin heavy chain (IgH) locus is critical for V region gene assembly. To determine Eµ's subsequent functions, we created an Igh allele with assembled VH gene but with Eµ removed. In mice homozygous for this Eµ-deficient allele, B cell development was normal and indistinguishable from that of mice with the same VH knockin and Eµ intact. In mice heterozygous for the Eµ-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 Eµ in influencing the fate of newly arising B cells and a second checkpoint for allelic exclusion.

Abbreviations used: 3' RR, 3' regulatory region; BCR, B cell receptor; ES, embryonic stem; IgH, Ig heavy chain; mRNA, messenger RNA.

© 2009 Li and Eckhardt This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jem.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).


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