IRF3-dependent type I interferon response in B cells regulates CpG-mediated antibody production.
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.
Oganesyan
Gagik
G
Department of Microbiology, Immunology and Molecular Genetics, University of California at Los Angeles, California 90095, USA.
Saha
Supriya K
SK
Pietras
Eric M
EM
Guo
Beichu
B
Miyahira
Andrea K
AK
Zarnegar
Brian
B
Cheng
Genhong
G
D000818:Animals; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000276:immunology*; D017931:DNA Primers; D003713:Dendritic Cells / Q000276:immunology; D015226:Dinucleoside Phosphates / Q000276:immunology*; D005434:Flow Cytometry; D050838:Interferon Regulatory Factor-3 / Q000502:physiology*; D007370:Interferon Type I / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D010766:Phosphorylation; D050794:STAT1 Transcription Factor / Q000378:metabolism
D017931:DNA Primers; D015226:Dinucleoside Phosphates; D050838:Interferon Regulatory Factor-3; D007370:Interferon Type I; D050794:STAT1 Transcription Factor; C015772:CpG dinucleotide