IgM是病原体侵入机体后免疫系统最初产生的抗体，是预防病毒和细菌感染的第一道防线。IgM不仅是效应分子，而且还可以通过活化补体促进体液免疫应答。我们最近克隆了IgM受体FcμR的基因，在国际上首次发现FcμR基因敲除小鼠有明显的免疫缺陷，同时还产生大量的自身抗体，提示FcμR既可促进适应性体液免疫，又抑制自身免疫，但是FcμR如何发挥其功能仍然不清楚。本项目拟对FcμR发挥功能的分子机制进行深入研究。在促进体液免疫方面，我们将研究FcμR和B细胞抗原受体（BCR）的信号传导的对话，理解FcμR特异性地促进抗原刺激后的B细胞生存的分子机制。同时，我们还将揭示FcμR和补体受体在促进体液免疫中的相对贡献。在研究抑制自身免疫方面，我们将重点研究FcμR诱导和维持B细胞自身耐受性的功能，阐明FcμR在清除和抑制自身反应性未成熟B细胞活化上的作用。本研究原创性高，且有广泛的临床应用潜能。

IgM is the first antibody isotype produced during an immune response and plays a crucial role in front line host defense against pathogens. In addition to its effector function, IgM has been shown to regulate humoral immune responses by activation of the classical complement pathway. We have recently identified the gene encoding the IgM Fc receptor (FcμR). We found that FcμR-deficient mice are immune deficient yet produce autoantibodies suggesting a role for FcμR in both humoral immunity against foreign antigens and tolerance to self-antigens. This project aims to elucidate the molecular mechanisms by which FcμR controls the homeostasis of the immune system. With regard to the FcμR-mediated enhancement of humoral immunity, we will analyze the cross talk between FcμR- and BCR-mediated signals and elucidate why FcμR is able to specifically enhance the survival of antigen-stimulated B cells. We will also explore whether FcμR and complement receptor, which is also required for efficient humoral immunity, function independently, or cooperate or compete with each other to regulate B cell immunity and tolerance. With regard to the autoantibody production, we will focus on the function of FcμR in the elimination or anergy of auto-reactive immature B cells. This highly creative and original project also has potential therapeutic applications in immunological disorders with altered IgM levels and in B-cell chronic lymphocytic leukemia where FcμR expression is elevated.