血清低糖基化IgA1（Gd-IgA1）分子是IgA肾病（IgAN）发病的重要启动因素，但其产生机制尚不清楚。FCRL3基因为IgAN的易感基因，其编码的蛋白可通过调控B细胞受体信号抑制B细胞的活化。新近，项目申请者发现IgAN患者B细胞FCRL3的表达显著降低，且与β-1,3半乳糖基转移酶C1GALT1及COSMC的表达水平呈正相关，与Gd-IgA1的表达水平呈负相关。此外，下调B细胞FCRL3表达可降低糖基转移酶的表达，以及增加Gd-IgA1的产生。因此，我们推测B细胞FCRL3表达降低可能通过促进B细胞的增殖分化，并调控糖基化转移酶的表达，使Gd-IgA1产生增加，导致IgAN发生。为此，本项目将以FCRL3+CD19+ B细胞为研究切入点，阐明其在IgAN患者中的表型特征和功能效应，研究B细胞FCRL3表达异常对Gd-IgA1产生的调控机制，为开发防治IgAN的新靶点提供科学依据。

Serum galactose-deficient IgA1 (Gd-IgA1) is an important trigger for the development of IgA nephropathy (IgAN), but the mechanism of its production remains unclear. FCRL3 gene is a susceptible gene for IgAN, and the protein encoded by FCRL3 can inhibit B cell activation by regulating B cell receptor signaling. Recently, we found that the expression levels of FCRL3 in B cells of IgAN patients were significantly decreased and positively correlated with the expression of β-1,3 galactosyltransferase C1GALT1 and COSMC, and were negatively correlated with the expression of serum Gd-IgA1. In addition, down-regulation of FCRL3 expression in B cells can decrease the expression levels of galactosyltransferase, and increase the production of Gd-IgA1. Therefore, we speculate that the decreased expression of FCRL3 in B cells may promote the proliferation and differentiation of B cells, and regulate the expression of glycosyltransferas, which can increase the production of Gd-IgA1, and lead to the occurrence of IgAN. This project takes FCRL3+CD19+ B cells as the starting point, to elucidate the phenotypic characteristics and functional effects of FCRL3+CD19+ B cells in IgAN patients, and study the role of abnormal FCRL3 expression in B cells on the production of Gd-IgA1, which could provide scientific evidence for the development of new targets for prevention and treatment of IgAN.