复旦大学王继扬教授
复旦大学基础医学院免疫学系王继扬教授课题组经3年攻关，找到被誉为机体预防病毒和细菌感染第一道防线的免疫球蛋白IgM的受体。IgM与受体结合后，不仅可以促进机体免疫功能增强，而且可以抑制自身有害抗体的产生，该研究对治疗人的免疫缺陷病和自身免疫疾病具有重大意义。目前，该成果相关论文已在线发表在《美国科学院院报》上。
免疫球蛋白是人体血液中存在的抗体，它具有清除机体内病原体的重要功能，而免疫球蛋白IgM是初次免疫应答中最早出现的抗体，是机体抗感染的“先头部队”。IgM抗体直接与病原体结合后可抑制病原体的活性，不让其发病、发展，并可通过特殊途径来融解病原体，阻止感染的扩大。早在40年前，世界各地的科学家就发现B淋巴细胞表面有IgM的受体，并有证据支持这一推断，但一直没有找到该受体。
王继扬教授课题组运用基因敲除技术成功培育了一种缺乏FcμR基因的敲除小鼠，并分析这种小鼠在缺乏该基因的状态下，在免疫功能和自身抗体方面会产生何种结果。经艰辛工作，研究人员终于首次发现了该受体的基因FcμR。研究发现，外来病原体侵入FcμR基因被敲除的小鼠后，出现明显的免疫缺陷状况，其抗体下降至正常小鼠的1/3以下。他们进一步研究发现，该免疫缺陷是由于FcμR基因敲除后，B淋巴细胞在受到外来病原体刺激后，不但不容易被激活，反而容易造成死亡。相反，缺乏FcμR基因的敲除小鼠在没有任何刺激的情况下，也会产生大量有害的自身抗体。
Critical role of the IgM Fc receptor in IgM homeostasis, B-cell survival, and humoral immune responses
Rika Ouchida, Hiromi Mori, Koji Hase, Hiroyuki Takatsu, Tomohiro Kurosaki, Takeshi Tokuhisa, Hiroshi Ohno, and Ji-Yang Wang
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 (FcμR) 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. FcμR did not affect steady-state B-cell survival but specifically enhanced the survival and proliferation induced by B-cell receptor cross-linking. Moreover, FcμR-deficient mice produced far more autoantibodies than control mice as they aged, suggesting that FcμR is also required for maintaining tolerance to self-antigens. Our results thus define a unique pathway mediated by the FcμR 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 FcμR.
文献链接：https://www.pnas.org/content/109/40/E2699.full?sid=6b3f94a1-5bfd-4c1d-bec9-8c379bff81fc
