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The Journal of Immunology, 2008, 180: 6725-6732.
Copyright © 2008 by The American Association of Immunologists, Inc.
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The Downstream Transcriptional Enhancer, Ed, Positively Regulates Mouse Ig{kappa} Gene Expression and Somatic Hypermutation1

Yougui Xiang and William T. Garrard2

Department of Molecular Biology University of Texas, Southwestern Medical Center, Dallas, TX 75390

The mouse Ig{kappa} locus has three known transcriptional enhancers: the matrix association region/intronic enhancer, the 3' enhancer (E3'), and the further downstream enhancer (Ed). Previous studies have shown that both matrix association region/intronic and E3' enhancers are required for maximal gene rearrangement of the locus, and that E3' is also required for maximal expression and somatic hypermutation (SHM). To functionally elucidate Ed in vivo, we generated knockout mice with a targeted germline deletion of Ed. Ed deleted homozygous mice (Ed–/–) have moderately reduced numbers of Ig{kappa} expressing B cells and correspondingly increased numbers of Ig{lambda} expressing B cells in spleen. Ed–/– mice also have decreased Ig{kappa} mRNA expression in resting and T cell-dependent activated splenic B cells and reduced Ig{kappa} chains in sera. However, our analysis indicates that Ig{kappa} gene rearrangement is normal in Ed–/– mice. In addition, our results show that Ed–/– mice exhibit reduced SHM in the Ig{kappa} gene J-C intronic region in germinal center B cells from Peyer’s patches. We conclude that Ed positively regulates Ig{kappa} gene expression and SHM, but not gene rearrangement.

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 Grants GM29935 and AI067906 from the National Institutes of Health and Grant I-0823 from the Robert A. Welch Foundation (to W.T.G.).

2 Address correspondence and reprint requests to Dr. William T. Garrard, Department of Molecular Biology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9148. E-mail address: william.garrard{at}utsouthwestern.edu

3 Abbreviations used in this paper: RSS, recombination signal sequence; GC, germinal center; SHM, somatic hypermutation; MAR, matrix association region; MEi, MAR/intronic enhancer; WT, wild type; ES, embryonic stem.


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