IRF3-dependent Type I Interferon Response in B Cells Regulates CpG-mediated Antibody Production*
- Gagik Oganesyan‡§,1,2,
- Supriya K. Saha‡§,1,2,
- Eric M. Pietras‡,
- Beichu Guo‡,
- Andrea K. Miyahira‡,
- Brian Zarnegar‡ and
- Genhong Cheng‡¶∥,3
- ‡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
- ↵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.
Abstract
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 June 11, 2007.
- Revision received October 9, 2007.
- The American Society for Biochemistry and Molecular Biology, Inc.
