RNA结合蛋白IGF2BP1/IGF2BP3调控CXCR5+淋巴细胞表型及功能的机制研究

CXCR5, the phenotypic marker expressing on follicular T helper (Tfh) cells and follicular regulatory T cells, is also the key factor closely related to the differentiation, maturation and function of Tfh and B cells. Its abnormal expression on Tfh and B cells resulted in the development of virus infection and various kinds of disease including tumor. RNA binding protein (RBP) plays a key role in controlling the gene expression but there has been no report about its influence on CXCR5. Our study first found two RBPs (IGF2BP1, IGF2BP3) binding to the RNA fragment of CXCR5. Based on the discovery, we explored the regulation of the RBPs on CXCR5 in B lymphoma cell line, in EBV immortalized cell model and in IGF2BP1 or IGF2BP3 knock-in mice models. The molecular mechanisms were further analyzed by screening the proteins interacting with IGF2BP1 or IGF2BP3. This study aims at getting a better understanding about the regulation of CXCR5 and the function of IGF2BP1 and IGF2BP3, also providing insights for the treatment of CXCR5+ lymphocytes associated diseases.

CXCR5是滤泡辅助性T细胞（Tfh）和滤泡调节性T细胞的表型特征分子，其表达水平是影响Tfh和B细胞分化、成熟及功能的重要因素。Tfh和B细胞表面CXCR5水平的异常与病毒感染以及肿瘤等多种疾病的发生发展密切相关。RNA结合蛋白（RBP）是影响基因表达水平的关键因素，目前尚无RBP调控CXCR5的报道。本研究首次发现IGF2BP1和IGF2BP3可与CXCR5的RNA结合，并基于此结合，在B淋巴瘤细胞系中、EBV感染介导的永生化细胞模型中、以及基因敲入的小鼠模型中，研究它们对CXCR5+ Tfh细胞和B细胞表型及功能的调控作用。通过筛选与IGF2BP1或IGF2BP3结合的蛋白，比较分析这两个蛋白调控CXCR5表达的具体分子机制。本研究旨在加深认识CXCR5的调控机制以及IGF2BP1和IGF2BP3的重要功能，为探索与CXCR5+淋巴细胞异常相关疾病的治疗策略提供理论依据。