Single-cell-level protein analysis revealing the roles of autoantigen-reactive B lymphocytes in autoimmune disease and the murine model.
Single-cell-level protein analysis revealing the roles of autoantigen-reactive B lymphocytes in autoimmune disease and the murine model.
复制标题
单细胞水平蛋白质分析揭示自身抗原反应性B淋巴细胞在自身免疫性疾病和小鼠模型中的作用
作者：
Fukasawa T;Yoshizaki A;Ebata S;Yoshizaki-Ogawa A;Asano Y;Enomoto A;Miyagawa K;Kazoe Y;Mawatari K;Kitamori T;Sato S
尽管B细胞的抗原亲和力因细胞而异，但由于技术困难，缺少单个B细胞上的抗原反应性B细胞的功能分析。特别是在自身免疫性疾病领域，有希望的致病性B细胞由于其稀有性迄今尚未得到充分研究。本研究从单细胞水平分析自身抗原反应性B细胞在自身免疫性疾病中的功能。由于拓扑异构酶I是一种独特的自身抗原，我们将系统性硬化症定位为自身免疫性疾病。拓扑异构酶I反应性B细胞对拓扑异构酶I的亲和力降低和增加导致抗炎和促炎细胞因子产生，其与纤维化的抑制和发展相关，纤维化是系统性硬化症的主要症状。此外，抑制促炎细胞因子的产生和增加拓扑异构酶I反应性B细胞的亲和力抑制纤维化。这些结果表明，自身抗原反应性B细胞通过其抗原亲和力促成自身免疫性疾病的疾病表现。
Despite antigen affinity of B cells varying from cell to cell, functional analyses of antigen-reactive B cells on individual B cells are missing due to technical difficulties. Especially in the field of autoimmune diseases, promising pathogenic B cells have not been adequately studied to date because of its rarity. In this study, functions of autoantigen-reactive B cells in autoimmune disease were analyzed at the single-cell level. Since topoisomerase I is a distinct autoantigen, we targeted systemic sclerosis as autoimmune disease. Decreased and increased affinities for topoisomerase I of topoisomerase I-reactive B cells led to anti-inflammatory and pro-inflammatory cytokine production associated with the inhibition and development of fibrosis, which is the major symptom of systemic sclerosis. Furthermore, inhibition of pro-inflammatory cytokine production and increased affinity of topoisomerase I-reactive B cells suppressed fibrosis. These results indicate that autoantigen-reactive B cells contribute to the disease manifestations in autoimmune disease through their antigen affinity.