title: IRF-2 regulates B-cell proliferation and antibody production through distinct mechanisms.
abstract: 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.
authors: Laboratory of Immunology, Department of Animal Development and Physiology, Division of Systemic Life Science, Graduate School of Biostudies, Kyoto University, Japan.
authors: Kento
authors: K
authors: Minamino
authors: Kazuhiko
authors: K
authors: Takahara
authors: Takumi
authors: T
authors: Adachi
authors: Koji
authors: K
authors: Nagaoka
authors: Tomonori
authors: T
authors: Iyoda
authors: Shinsuke
authors: S
authors: Taki
authors: Kayo
authors: K
authors: Inaba
mesh_terms: D000818:Animals; D000917:Antibody Formation / Q000235:genetics; D001402:B-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D002454:Cell Differentiation / Q000235:genetics; D049109:Cell Proliferation; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D017578:Immunoglobulin Class Switching / Q000235:genetics; D007148:Immunoglobulin mu-Chains / Q000235:genetics; D050836:Interferon Regulatory Factor-2 / Q000235:genetics / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010950:Plasma Cells / Q000276:immunology* / Q000637:transplantation; D000074462:Positive Regulatory Domain I-Binding Factor 1; D053633:Receptor, Interferon alpha-beta / Q000378:metabolism*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D007148:Immunoglobulin mu-Chains; D050836:Interferon Regulatory Factor-2; D008070:Lipopolysaccharides; C513258:Prdm1 protein, mouse; D014157:Transcription Factors; D053633:Receptor, Interferon alpha-beta; D000074462:Positive Regulatory Domain I-Binding Factor 1