This Article Full Text Full Text (PDF) Other Versions of this Article: MCB.01946-07v1 28/8/2815    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Google Scholar Articles by Pathak, S. Articles by Lu, R. PubMed PubMed Citation Articles by Pathak, S. Articles by Lu, R.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, April 2008, p. 2815-2824, Vol. 28, No. 8
0270-7306/08/$08.00+0     doi:10.1128/MCB.01946-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

A Role for Interferon Regulatory Factor 4 in Receptor Editing

Department of Genetics, Cell Biology, and Anatomy, University of Nebraska Medical Center, Omaha, Nebraska 68198

Received 29 October 2007/ Returned for modification 16 November 2007/ Accepted 6 February 2008

Receptor editing is the primary means through which B cells revise antigen receptors and maintain central tolerance. Previous studies have demonstrated that interferon regulatory factor 4 (IRF-4) and IRF-8 promote immunoglobulin light-chain rearrangement and transcription at the pre-B stage. Here, the roles of IRF-4 and -8 in receptor editing were analyzed. Our results show that secondary rearrangement was impaired in IRF-4 but not IRF-8 mutant mice, suggesting that receptor editing is defective in the absence of IRF-4. The role of IRF-4 in receptor editing was further examined in B-cell-receptor (BCR) transgenic mice. Our results show that secondary rearrangement triggered by membrane-bound antigen was defective in the IRF-4-deficient mice. Our results further reveal that the defect in secondary rearrangement is more severe at the immunoglobulin locus than at the locus, indicating that IRF-4 is more critical for the rearrangement. We provide evidence demonstrating that the expression of IRF-4 in immature B cells is rapidly induced by self-antigen and that the reconstitution of IRF-4 expression in the IRF-4 mutant immature B cells promotes secondary rearrangement. Thus, our studies identify IRF-4 as a nuclear effector of a BCR signaling pathway that promotes secondary rearrangement at the immature B-cell stage.

Published ahead of print on 19 February 2008.