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

First Author  Minamino K Year  2012
Journal  Int Immunol Volume  24
Issue  9 Pages  573-81
PubMed ID  22773153 Mgi Jnum  J:187171
Mgi Id  MGI:5435632 Doi  10.1093/intimm/dxs060
Citation  Minamino K, et al. (2012) IRF-2 regulates B-cell proliferation and antibody production through distinct mechanisms. Int Immunol 24(9):573-81
abstractText  Interferon regulatory factor (IRF)-2 is a transcription factor involved in type I (IFN- alpha/beta) 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- alpha/beta 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 micro 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.
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