Critical role of the IgM Fc receptor in IgM homeostasis, B-cell survival, and humoral immune responses
Critical role of the IgM Fc receptor in IgM homeostasis, B-cell survival, and humoral immune responses
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DOI：
10.1073/pnas.1210706109
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发表时间：
2012-10-02
影响因子：
11.1
通讯作者：
Wang, Ji-Yang
中科院分区：
文献类型：
--
作者：
Ouchida, Rika;Mori, Hiromi;Wang, Ji-Yang
几十年来，IgM抗体以抗原特异性的方式增强体液免疫反应。这种增强被认为依赖于igm抗原复合物的补体活化；然而，最近的基因研究表明这种机制不太可能。在这里，我们描述了一个可能的替代解释；在B细胞上缺乏最近发现的IgM Fc受体（Fc mu R）的小鼠在原发性和记忆反应中产生的蛋白抗原抗体显著减少。这种免疫缺陷伴随着生发中心形成受损，血浆和记忆b细胞生成减少。Fc mu R不影响稳态b细胞的存活，但能特异性增强b细胞受体交联诱导的存活和增殖。此外，随着年龄的增长，Fc mu R缺陷小鼠产生的自身抗体远远多于对照组小鼠，这表明Fc mu R也是维持对自身抗原耐受性所必需的。因此，我们的研究结果定义了一种由Fc mu R介导的调节免疫和耐受性的独特途径，并表明IgM抗体通过补体激活和Fc mu R至少两种途径促进对外来抗原的体液免疫反应，同时抑制自身抗体的产生。
IgM antibodies have been known for decades to enhance humoral immune responses in an antigen-specific fashion. This enhancement has been thought to be dependent on complement activation by IgM-antigen complexes; however, recent genetic studies render this mechanism unlikely. Here, we describe a likely alternative explanation; mice lacking the recently identified Fc receptor for IgM (Fc mu R) on B cells produced significantly less antibody to protein antigen during both primary and memory responses. This immune deficiency was accompanied by impaired germinal center formation and decreased plasma and memory B-cell generation. Fc mu R did not affect steady-state B-cell survival but specifically enhanced the survival and proliferation induced by B-cell receptor cross-linking. Moreover, Fc mu R-deficient mice produced far more autoantibodies than control mice as they aged, suggesting that Fc mu R is also required for maintaining tolerance to self-antigens. Our results thus define a unique pathway mediated by the Fc mu R for regulating immunity and tolerance and suggest that IgM antibodies promote humoral immune responses to foreign antigen yet suppress autoantibody production through at least two pathways: complement activation and Fc mu R.