Journal Article

IRF-2 regulates B-cell proliferation and antibody production through distinct mechanisms

Kento Minamino, Kazuhiko Takahara, Takumi Adachi, Koji Nagaoka, Tomonori Iyoda, Shinsuke Taki and Kayo Inaba

in International Immunology Meeting Abstracts

Published on behalf of Japanese Society for Immunology

Volume 24, issue 9, pages 573-581
Published in print September 2012 |
Published online July 2012 | | DOI: http://dx.doi.org/10.1093/intimm/dxs060

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Interferon regulatory factor (IRF)-2 is a transcription factor involved in type I (IFN- α/β) signaling. It has been reported that IRF-2 deficiency results in various immune dysfunctions. However, the role of IRF-2 in B-cell functions needs to be elucidated. Unlike wild-type (WT) B cells, IRF-2-/- B2 cells were refractory to anti-IgM, but not LPS. Such a defect in proliferation was dependent on IFN- α/β receptor (IFNAR). Marginal zone B cells increased in the proportion relative to B2 cells in IRF-2-/- mice produced IgM normally to LPS stimulation. However, IRF-2-/- B2 cells were defective in IgM production in an IFNAR-independent manner, although both B-cell subsets differentiated phenotypically to plasma cells at elevated efficiencies. Class switch recombination of IRF-2-/- B2 cells by LPS plus IL-4 was also impaired. Their reduced IgM production was conceivably due to an inefficient up-regulation of Blimp-1. Consistent with these in vitro observations, specific antibody production in vivo to a T-dependent antigen by B2 cells was severely impaired in IRF-2-/- mice. However, a low, but significant, level of IgG was detected at a late time point, and this IgG exhibited comparable binding affinity to that in WT mice. Follicular helper T-cell development and germinal center formation were normal. A similar tendency was observed when µ chain-/- mice were reconstituted with IRF-2-/- B cells. These results revealed a multi-faceted role of IRF-2 in the function of B cells, particularly B2 cells, through regulating proliferation in an IFNAR-dependent manner and antibody production via up-regulation of Blimp-1.

Keywords: activation; antibody production; B cells; differentiation; interferon regulatory factor-2

Journal Article.  6221 words.  Illustrated.

Subjects: Immunology ; Biochemical Immunology

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