ERp72通过调控HSP90β蛋白二硫键形成进而调控BCR信号和B细胞体液免疫应答的机制研究

ERp72的异常表达参与多种疾病的发生，但其在免疫系统中尤其是在B细胞中的作用还不清楚。通过构建Erp72 KO小鼠我们发现，在ERp72缺失小鼠中，骨髓再循环B细胞亚群减少, 外周FO、T1、MZ和GC B细胞以及B1a和B1b细胞分化紊乱。同时BCR信号和B细胞体液免疫应答均降低。但ERp72调控BCR信号，B细胞分化和体液免疫应答的具体机制还不清楚。另外， ERp72缺失的B 细胞Hsp90ab1的mRNA水平不变，但其蛋白水平降低。而在WT B细胞中HSP90β与ERp72具有相互作用。但ERp72如何调控HSP90β的蛋白表达进而调控B细胞功能的机制还有待阐明。本研究拟通过Erp72 敲除小鼠模型，并结合免疫学、细胞生物学和分子生物学对上述问题进行深入解析。该研究将最终阐明ERp72调控B细胞功能的分子机制，同时也为探究ERp72异常表达参与多种疾病发生的机制研究提供理论基础。

The abnormal expression of ERp72 is involved in the occurrence of many diseases, but its role in the immune system, especially in B cells, is still unclear. By constructing Erp72 KO mice, we found that in ERp72-deficient mice, the recirculating B cell subsets in the bone marrow were reduced, and the FO, T1, MZ and GC B cell subsets in the spleen and the B1a and B1b cell subsets in the abdominal cavity were differentiated disorderly. Further research found that the BCR signal and B cell humoral immune response were reduced. But the specific mechanism of ERp72 regulating BCR signal, B cell differentiation and humoral immune response is still unclear. In addition, the mRNA level of Hsp90ab1 in ERp72-deficient B cells remains unchanged, but its protein level is reduced. And HSP90β interacts with ERp72 in WT B cells. However, the mechanism of how ERp72 regulates the protein expression of HSP90β and then regulates BCR signaling, B cell differentiation and function remains to be elucidated. In this study, we will use the Erp72 knockout mouse and combine immunology, cell biology and molecular biology to analyze the above questions in depth. This research will finally clarify the molecular mechanism of ERp72 regulating B cell function, and also provide a theoretical basis for exploring the mechanism of abnormal expression of ERp72 in the occurrence of various diseases.