Gm614（Cxorf65）在自身免疫病生发中心B细胞中的作用及机制

目前对自身免疫病生发中心（GC）反应是如何影响自身抗体产生及特性这一关键事件仍不甚清楚。本课题组在前期研究基础上，提出以下科学假设：自身免疫病促进GC反应中B细胞表达新分子(小鼠Gm614和人Cxorf65是同源基因)，此同源蛋白定位在细胞核，作为转录激活因子促进Aid等分子表达，从而增强自身反应性GC B细胞中自身抗体类别转换并可能影响自身抗体亲和力、多样性等，进而促进高致病性高亲和力自身抗体产生并介导自身免疫病的发生、发展。本项目拟通过小鼠体内外与自身免疫病人细胞体外实验，分别阐明Gm614和Cxorf65对自身反应性GC B细胞增殖，自身抗体类别转换重组、点突变及亲和力等的影响，揭示新分子Gm614（Cxorf65）在自身反应性GC B细胞调控自身抗体产生及特性中的作用机制。本项目的研究将有助于深入了解系统性红斑狼疮和多发硬化发生、发展的免疫学机制并为相关自身免疫病干预提供实验依据。

Currently, it is still unclear how the germinal center (GC) response affects the production and characteristics of autoantibody in autoimmune diseases. Based on our previous research, we proposed the following scientific hypothesis: Autoimmune diseases promote the expression of new molecules (mouse Gm614 and human Cxorf65 are homologous genes) in GC B cells. This homologous protein is located in the nucleus and acts as a transcriptional activation Factors to promote the expression of Aid and other molecules. Aid and other molecules enhance class switching of autoantibodies in autoreactive GC B cells and may affect autoantibody affinity, diversity, etc. Those events promote the production of highly pathogenic high-affinity autoantibodies that mediates the occurrence and development of autoimmune diseases. This project intends to clarify the effects of Gm614 and Cxorf65 on the proliferation of autoreactive GC B cells, autoantibody class, point mutations and affinity, etc., through in vitro and in vivo mice experiments and in vitro experiments of cells from autoimmune patients, respectively. It is explored to the mechanisms by which Gm614 (Cxorf65) regulates the production and characteristics of autoantibodies in autoreactive GC B cells. The project will help to deeply understand the immunological mechanism of the occurrence and development of systemic lupus erythematosus and multiple sclerosis and provide experimental basis for the intervention of autoimmune diseases.