干燥综合征（pSS）是一种与B细胞过度活化相关的自身免疫性疾病。据报道，自身免疫调节因子（AIRE）缺陷能够诱导小鼠pSS发病，但具体机制尚不明确。我们初步研究发现，与健康对照人群相比，pSS患者B细胞内AIRE表达明显下降。激活诱导的胞嘧啶脱氨酶(AID)是介导B细胞被激活后，发生抗体亲和力成熟和类别转化的必需酶。我们还观察到，AIRE与AID共表达于滤泡B细胞内并且有相互作用。此外与Aire+/+相比，Aire−/−B细胞内AID活性显著增强。因此我们提出：AIRE缺陷，导致AID功能亢进和B细胞过度激活，诱发pSS的科学假说。本项目将重点研究B细胞活化过程中，AIRE对AID介导的体细胞超突变和抗体类别转化重组的影响和分子机制，阐明Aire对AID的调控在B细胞参与pSS发病中所起的作用，为进一步揭示pSS的致病机理，探索针对AIRE/AID为靶点的新型治疗手段，提供可靠的科学依据。

Primary Sjogern's Syndrome (pSS) is a common autoimmune disease characterized by aberrant activation of B cells. It has been reported that mice with deficiency of autoimmune regulator (AIRE) can induce pSS, but the detailed mechanism remains unclear. Our preliminary data showed that AIRE expression is significantly reduced in B cells from pSS patients as compared to the health control. Activation-induced cytidine deaminase (AID) plays a critical role in initiating and mediating somatic hypermutation (SHM) and class switch recombination (CSR) during antibody affinity maturation. In preliminary study, we also observed that AIRE and AID present in the same follicular B cells and interact each other. In addition, the ratios of SHM and CSR that reflect the activity of AID are significantly higher in Aire−/− as compared to Aire+/+ B cells upon stimulation. Hereby, we hypothesize that AIRE deficiency results in aberrant activation of AID and B cells, thus promoting the pathogenesis of pSS. The project will focus on exploring the interaction between AIRE and AID as well as its effect on regulating SHM and CSR mediated by AID in activated B cells. Such study is essential to further unveil the molecular mechanism for the pathogenesis of pSS and provide insights into developing novel therapeutic approaches for pSS by targeting on the AIRE/AID pathway.