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Title: IRF-2 regulates B-cell proliferation and antibody production through distinct mechanisms.
Authors: Minamino, Kento
Takahara, Kazuhiko  kyouindb  KAKEN_id  orcid https://orcid.org/0000-0003-4730-8187 (unconfirmed)
Adachi, Takumi
Nagaoka, Koji
Iyoda, Tomonori
Taki, Shinsuke
Inaba, Kayo  kyouindb  KAKEN_id
Author's alias: 稲葉, カヨ
Keywords: activation
antibody production
B cells
differentiation
interferon regulatory factor-2
Issue Date: 5-Jul-2012
Publisher: Oxford University Press
Journal title: International immunology
Volume: 24
Issue: 9
Start page: 573
End page: 581
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.
Rights: © The Author 2012. Published by Oxford University Press.
This is not the published version. Please cite only the published version. この論文は出版社版でありません。引用の際には出版社版をご確認ご利用ください。
URI: http://hdl.handle.net/2433/176343
DOI(Published Version): 10.1093/intimm/dxs060
PubMed ID: 22773153
Appears in Collections:Journal Articles

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