Molecular base of the defenses against infection by IgM and IgA

IgM通过启动经典的补体级联反应在天然免疫中起关键作用。近年来，一种新的IgM和伊加Fc受体（Fcα/μR）被克隆，但其在IgM介导的免疫中的作用尚不清楚。在这里，我们发现边缘区B（MZ B）细胞和滤泡树突状细胞（FDC）优先表达Fcα/μR。在Fcα/μ R缺陷小鼠中，尽管对TD抗原的GC形成正常，但对TI抗原的GC形成增强，其中B细胞和FDC均参与。抗原-IgM复合物的形成通过IgM-Fcα/μR相互作用减少BCR介导的活化和B细胞的补体依赖性抗原沉积。Fcα/μ R缺陷小鼠显示MZB细胞和FDC的抗原保留增强，淋巴器官中的CXCL 13表达响应于TI抗原。此外，在Fcα/μ R缺陷小鼠中，TI抗原诱导的GC形成导致IgG 3的亲和力成熟。消除补体途径完全减弱这些表型。总体而言，Fcα/μR可能通过与补体级联反应相互作用，对IgM介导的抗TI抗原免疫应答发挥微调机制。

IgM plays pivotal role in innate immunity by initiating classical complement cascade. Recently, an novel Fc receptor for IgM and IgA, Fcα/μR, was finaly cloned, but its involvement in IgM-mediated immunity was unclear. Here, we show that marginal zone B (MZB) cells and follicular dendritic cells (FDC) preferentially express Fcα/μR. In Fcα/μR-deficient mice, although GC formation against TD antigen was normal, that against TI antigen was enhanced, in which both B cells and FDC were involved. Formation of antigen-IgM complex decreased BCR-mediated activation and complement dependent antigen deposition of B cells via IgM-Fcα/μR interaction. Fcα/μR-deficient mice showed enhanced antigen retention by MZB cells and FDC, and CXCL13 expression in lymphoid organ in response to TI antigen. Moreover, TI antigen induced GC formation in Fcα/μR-deficient mice result in the affinity maturation of IgG3. Abrogation of complement pathway completely attenuated these phenotypes. Collectively, Fcα/μR may exert fine-tuning mechanism of IgM-mediated immune responses against TI antigens by interacting with the complement cascades.