Laboratory of Immunology, Department of Animal Development and Physiology, Division of Systemic Life Science, Graduate School of Biostudies, Kyoto University, Japan.
Int Immunol. 2012 Sep;24(9):573-81. doi: 10.1093/intimm/dxs060. Epub 2012 Jul 5.
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.
干扰素调节因子 (IRF)-2 是一种参与 I 型 (IFN-α/β) 信号转导的转录因子。据报道，IRF-2 缺陷导致各种免疫功能障碍。然而，IRF-2 在 B 细胞功能中的作用仍需阐明。与野生型 (WT) B 细胞不同，IRF-2(-/-) B2 细胞对抗 IgM 但不对 LPS 产生反应。这种增殖缺陷依赖于 IFN-α/β受体 (IFNAR)。IRF-2(-/-) 小鼠中相对 B2 细胞增加的边缘区 B 细胞对 LPS 刺激正常产生 IgM。然而，IRF-2(-/-) B2 细胞以 IFNAR 非依赖性方式在 IgM 产生中存在缺陷，尽管两个 B 细胞亚群在效率提高的情况下分化为浆细胞。IRF-2(-/-) B2 细胞通过 LPS 加 IL-4 的类别转换重组也受损。它们减少的 IgM 产生可能是由于 Blimp-1 的上调效率低下。与这些体外观察结果一致，在 IRF-2(-/-) 小鼠中，B2 细胞对 T 依赖性抗原的体内特异性抗体产生严重受损。然而，在后期检测到低但有意义的 IgG 水平，并且该 IgG 表现出与 WT 小鼠相当的结合亲和力。滤泡辅助 T 细胞发育和生发中心形成正常。当用 IRF-2(-/-) B 细胞重建 µ 链(-/-) 小鼠时，观察到类似的趋势。这些结果表明，IRF-2 通过 IFNAR 依赖性方式调节增殖和通过上调 Blimp-1 调节抗体产生，在 B 细胞特别是 B2 细胞的功能中发挥多方面作用。
