IRF-2 regulates B-cell proliferation and antibody production through distinct mechanisms.
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抄録
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.
収録刊行物
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- International immunology
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International immunology 24 (9), 573-581, 2012-07-05
Oxford University Press
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キーワード
- activation
- antibody production
- B cells
- differentiation
- interferon regulatory factor-2
- Animals
- Antibody Formation/genetics
- B-Lymphocytes/immunology
- B-Lymphocytes/transplantation
- Cell Differentiation/genetics
- Cell Proliferation
- Cells, Cultured
- Gene Expression Regulation
- Immunoglobulin Class Switching/genetics
- Immunoglobulin mu-Chains/genetics
- Interferon Regulatory Factor-2/genetics
- Interferon Regulatory Factor-2/metabolism
- Lipopolysaccharides/immunology
- Mice
- Mice, Inbred C57BL
- Mice, Knockout
- Plasma Cells/immunology
- Plasma Cells/transplantation
- Receptor, Interferon alpha-beta/metabolism
- T-Lymphocytes, Helper-Inducer/immunology
- Transcription Factors/genetics
- Transcription Factors/metabolism
詳細情報 詳細情報について
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- CRID
- 1050564285725968512
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- NII論文ID
- 120005302075
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- ISSN
- 14602377
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- HANDLE
- 2433/176343
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- 本文言語コード
- en
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- 資料種別
- journal article
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- データソース種別
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- IRDB
- CiNii Articles