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标题：Critical role of IRF-5 in regulation of B-cell differentiation
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作者：Chunyang Lien ; Chee-Mun Fang ; David Huso 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2010
卷号：107
期号：10
页码：4664-4668
DOI：10.1073/pnas.0911193107
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：IFN-regulatory factor 5 (IRF-5), a member of the IRF family, is a transcription factor that has a key role in the induction of the antiviral and inflammatory response. When compared with C57BL/6 mice, Irf5-/- mice show higher susceptibility to viral infection and decreased serum levels of type I IFN and the inflammatory cytokines IL-6 and TNF-{alpha}. Here, we demonstrate that IRF-5 is involved in B-cell maturation and the stimulation of Blimp-1 expression. The Irf5-/- mice develop an age-related splenomegaly, associated with a dramatic accumulation of CD19+B220- B cells and a disruption of normal splenic architecture. Splenic B cells from Irf5-/- mice also exhibited a decreased level of plasma cells. The CD19+ Irf5-/- B cells show a defect in Toll-like receptor (TLR) 7- and TLR9-induced IL-6 production, and the aged Irf5-/- mice have decreased serum levels of natural antibodies; however, the antigen-specific IgG1 primary response was already dependent in IRF-5 in young mice, although the IgM response was not. Analysis of the profile of transcription factors associated with plasma cell differentiation shows down-regulation of Blimp-1 expression, a master regulator of plasma cell differentiation, which can be reconstituted with ectopic IRF-5. IRF-5 stimulates transcription of the Prdm1 gene encoding Blimp-1 and binds to the IRF site in the Prdm1 promoter. Collectively, these results reveal that the age-related splenomegaly in Irf5-/- mice is associated with an accumulation of CD19+B220- B cells with impaired functions and show the role of IRF-5 in the direct regulation of the plasma cell commitment factor Blimp-1 and in B-cell terminal differentiation.
关键词：IRF-5 ; antigenic response ; B-cell development ; Blimp-1 ; Toll-like receptors