HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 283, Issue 2, 802-808, January 11, 2008

This Article Full Text Full Text (PDF) All Versions of this Article: 283/2/802    most recent M704755200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted 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 Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Oganesyan, G. Articles by Cheng, G. Search for Related Content PubMed PubMed Citation Articles by Oganesyan, G. Articles by Cheng, G. Social Bookmarking                      What's this?

IRF3-dependent Type I Interferon Response in B Cells Regulates CpG-mediated Antibody Production^*

Gagik Oganesyan¹², Supriya K. Saha¹², Eric M. Pietras, Beichu Guo, Andrea K. Miyahira, Brian Zarnegar, and Genhong Cheng^¶||3

From the Department of Microbiology, Immunology and Molecular Genetics, Medical Scientist Training Program, ^¶Molecular Biology Institute, and ^||Jonsson Comprehensive Cancer Center, University of California at Los Angeles, Los Angeles, California 90095

Hypomethylated CpG oligonucleotides (CpG) are not only potent adjuvants for enhancing adaptive immune responses but may also play a critical role in the development of autoimmune diseases such as Rheumatoid Arthritis (RA) and Systemic Lupus Erythematosus (SLE). Here we provide evidence that, in addition to dendritic cells, murine B lymphocytes also exhibit a type I IFN response to CpG-B. Unlike dendritic cells, B cell-mediated type I IFN induction depended on the transcription factor IRF3, but similar to dendritic cells this pathway was independent of the IRF3 kinase TBK1. Utilizing type I IFN receptor-deficient mice, we were able to demonstrate that this IFN pathway enhanced Syndecan-1 expression and IgM production and was required for IgG2a production following CpG-B stimulation. Overall, our findings identify a unique IFN pathway in B cells that may play a central role in mediating B cell biology in response to CpG, potentially implicating this pathway in autoantibody production and the pathogenesis of certain autoimmune diseases.

Received for publication, June 11, 2007 , and in revised form, October 9, 2007.

^* This work was supported in part by National Institutes of Health Research Grants R01 AI056154, R01 CA87924, and R01 GM57559. 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 Both authors contributed equally to this article.

² Supported by UCLA Medical Scientist Training Program Training Grant GM 08042.

³ To whom correspondence should be addressed: Dept. of Microbiology, Immunology and Molecular Genetics, University of California at Los Angeles, 8-240 Factor Bldg., 10833 Le Conte Ave., Los Angeles, CA 90095. Tel.: 310-825-8896; Fax: 310-206-5553; E-mail: gcheng{at}mednet.ucla.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?