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Blood, 1 December 2006, Vol. 108, No. 12, pp. 3769-3776. Prepublished online as a Blood First Edition Paper on August 8, 2006; DOI 10.1182/blood-2006-03-008839. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-03-008839v1 108/12/3769    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Lu, K. T. Articles by Covey, L. R. Search for Related Content PubMed PubMed Citation Articles by Lu, K. T. Articles by Covey, L. R. Related Collections Immunobiology Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY c-Rel plays a key role in deficient activation of B cells from a non–X-linked hyper-IgM patient Kristina T. Lu, Frank L. Sinquett, Rebecca L. Dryer, Charles Song, and Lori R. Covey From the Department of Cell Biology and Neuroscience, Rutgers, The State University of New Jersey, Piscataway; and Harbor General Hospital, University of California–Los Angeles, Torrance. Our previous results demonstrated that B cells from a patient (pt1) with non–X-linked hyper-IgM syndrome (HIGM) possess an atypical CD23lo phenotype that is unaffected by CD40-mediated activation. To investigate the molecular mechanism underlying defective CD23 expression in pt1 B cells, we used lymphoblastoid cell lines that express LMP1 under the control of a tetracycline-inducible promoter (LCLtet). Our analysis revealed that the CD23lo phenotype in the pt1-LCLtet cells is a direct consequence of diminished CD23 transcription. We demonstrate a marked decrease in c-Rel–containing complexes that bind to the proximal CD23a/b promoters in pt1-LCLtet extracts, resulting from an overall lower expression of c-Rel in pt1-LCLtet cells. Analysis of c-Rel mRNA revealed relatively equal amounts in pt1-LCLtet and control LCLtet cells, indicating that diminished c-Rel protein expression is unrelated to decreased transcription. Finally, a critical role for c-Rel in CD23 regulation was demonstrated by effectively altering c-Rel expression that resulted in the direct modulation of CD23 surface expression. Collectively, these findings demonstrate that low levels of c-Rel are the underlying cause of aberrant CD23 expression in pt1 B cells and are likely to play a critical role in the pathophysiology of this form of HIGM. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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