B细胞同时表达活化性IgM受体(FcμR)和抑制性IgG受体(FcγRⅡB)。本研究的目的是阐明IgM和IgG抗体如何分别通过FcμR和FcγRⅡB调节B细胞生存和活化，维持体液免疫平衡，抑制自身免疫。我们将详细分析IgM/FcμR和IgG/FcγRⅡB通路与BCR信号通路的crosstalk。我们将借助人的高免疫球蛋白M综合征(HIGM)疾病模型Aicda-/-鼠，系统性红斑狼疮(SLE)疾病模型FcγRⅡB-/-鼠，免疫缺陷FcμR-/-小鼠，以及交配这些小鼠得到的FcμR-/- Aicda-/-和FcμR-/-×FcγRⅡB-/- 双敲模型鼠，揭示IgM/FcμR和IgG/FcγRⅡB通路在体内维持体液免疫平衡抑制自身免疫中的相互作用。本项目创新性高，其研究成果将有助于理解HIGM以及SLE等伴随抗体产生异常的免疫疾病的发病机理，同时为探索新的治疗方法提供新的思路。

B cells express both the activating IgM Fc receptor (FcμR) and the inhibitory IgG Fc receptor (FcγRIIB). The aim of this project is to elucidate the mechanisms by which IgM/FcμR and IgG/FcγRIIB regulate B cell survival and activation, maintain immune balance and suppress autoimmunity. We will analyze the crosstalk between IgM/FcμR and IgG/FcγRIIB pathways in regulating B cell receptor (BCR) signaling. In addition, we will use Aicda-/- mice, a model for the human primary immunodeficiency disease hyper-IgM syndrome (HIGM) and FcγRIIB-/- mice, a model of the systemic lupus erythematosus (SLE). We will establish FcμR-/-Aicda-/- and FcμR-/-FcγRIIB-/- mice to investigate whether eliminating the IgM/FcμR-mediated activating signal can suppress excessive B cell activation and autoimmune disease in these mouse models. The results of this highly creative project should accelerate our understanding of the etiology of immunological disorders associated with altered IgM/IgG production, such as HIGM and SLE, and provide new insights for potential therapeutic intervention.