Single-cell-level protein analysis revealing the roles of autoantigen-reactive B lymphocytes in autoimmune disease and the murine model

eLife

Kazuma Mawatari¹  Ayumi Yoshizaki²  Asako Yoshizaki-Ogawa²  Shinichi Sato²  Satoshi Ebata²  Yoshihide Asano²  Takemichi Fukasawa²  Takehiko Kitamori³  Yutaka Kazoe⁴  Atsushi Enomoto⁵  Kiyoshi Miyagawa⁵ 

[1] Department of Applied Chemistry, The University of Tokyo Graduate School of Engineering, Tokyo, Japan;Department of Dermatology, The University of Tokyo Graduate School of Medicine, Tokyo, Japan;Department of Mechanical Engineering, The University of Tokyo Graduate School of Engineering, Tokyo, Japan;Department of System Design Engineering, Keio university, Faculty of Science and technology, Tokyo, Japan;Laboratory of Radiology and Biomedical Engineering, The University of Tokyo Graduate School of Medicine, Tokyo, Japan;

关键词: B cell;    systemic sclerosis;    fibrosis;    single cell analysis;    cytokine;    Human;    Mouse;   

DOI  :  10.7554/eLife.67209

来源: eLife Sciences Publications, Ltd

【 摘 要 】

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.

【 授权许可】

CC BY