B细胞分泌的IFNγ在CD11c+ B细胞发育中的重要作用

自身免疫病严重危害人类健康，发病机制尚不明确。近年来新发现的一群CD11c+B细胞被认为与自身免疫病的发生极具相关性。本课题组的已发表研究成果表明，在自身免疫病中，过量的CD11c+B细胞可以引起TFH细胞的过量分化并导致抗体亲和力成熟过程的抑制。在小鼠自身免疫病模型中抑制CD11c+B细胞的生成，可以有效的抑制自身免疫病的发生发展，使得这群CD11c+B细胞极有可能成为治疗自身免疫性疾病的有效靶点。然而，对于这一细胞亚群的来源以及分化，尚不明确。我们的前期研究结果显示，CD11c+B细胞可以分泌IFNγ，IFNγ基因敲除可以有效抑制CD11c+B细胞的产生。这提示，B细胞分泌的IFNγ在CD11c+B细胞分化中发挥着重要作用。本项目的实施将进一步理清CD11c+B细胞的分化路径，为CD11c+B细胞的更深入研究提供理论和实验依据，为自身免疫病的靶向治疗策略提供一个新的方向。

Autoimmune diseases seriously harm human health, and the pathogenesis still needs further research. CD11c+ B cells, which is a newly defined B cell subpopulation in recent years, are considered to be highly correlated with the occurrence of autoimmune diseases. Our study have demonstrated that excessive CD11c+ B cells promoted aberrant TFH differentiation and affinity-based germinal center selection in autoimmune disease. Inhibiting the differentiation of CD11c+ B cells in autoimmune disease models can effectively inhibit the occurrence and development of autoimmune diseases, making these CD11c+ B cells most likely to become an effective target for the treatment of autoimmune diseases. However, the source and differentiation of these CD11c+ B cells is not yet clear. IFNγ receptor signaling has been reported to be important for the differentiation of these CD11c+ B cells. Our previous results showed that IFNγ can be secreted by CD11c+ B cells and IFNγ gene deletion can effectively inhibit the production of CD11c+ B cells. These results suggest that IFNγ secreted by B cells plays an important role in CD11c+ B cell differentiation. This project will further clarify the differentiation pathway of CD11c+ B cells, provide theoretical and experimental basis for the further study of CD11c+ B cells, and provide a new direction for the targeted treatment strategy of autoimmune diseases.