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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.<\/jats:p>","DOI":"10.7554\/elife.67209","type":"journal-article","created":{"date-parts":[[2021,11,22]],"date-time":"2021-11-22T08:15:16Z","timestamp":1637568916000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.67209","source":"Crossref","is-referenced-by-count":47,"title":["Single-cell-level protein analysis revealing the roles of autoantigen-reactive B lymphocytes in autoimmune disease and the murine model"],"prefix":"10.7554","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6093-1881","authenticated-orcid":true,"given":"Takemichi","family":"Fukasawa","sequence":"first","affiliation":[{"name":"Department of Dermatology, The University of Tokyo Graduate School of Medicine","place":["Tokyo, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8194-9140","authenticated-orcid":true,"given":"Ayumi","family":"Yoshizaki","sequence":"additional","affiliation":[{"name":"Department of Dermatology, The University of Tokyo Graduate School of Medicine","place":["Tokyo, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Ebata","sequence":"additional","affiliation":[{"name":"Department of Dermatology, The University of Tokyo Graduate School of Medicine","place":["Tokyo, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asako","family":"Yoshizaki-Ogawa","sequence":"additional","affiliation":[{"name":"Department of Dermatology, The University of Tokyo Graduate School of Medicine","place":["Tokyo, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihide","family":"Asano","sequence":"additional","affiliation":[{"name":"Department of Dermatology, The University of Tokyo Graduate School of Medicine","place":["Tokyo, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsushi","family":"Enomoto","sequence":"additional","affiliation":[{"name":"Laboratory of Radiology and Biomedical Engineering, The University of Tokyo Graduate School of Medicine","place":["Tokyo, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiyoshi","family":"Miyagawa","sequence":"additional","affiliation":[{"name":"Laboratory of Radiology and Biomedical Engineering, The University of Tokyo Graduate School of Medicine","place":["Tokyo, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yutaka","family":"Kazoe","sequence":"additional","affiliation":[{"name":"Department of System Design Engineering, Keio university, Faculty of Science and technology","place":["Tokyo, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuma","family":"Mawatari","sequence":"additional","affiliation":[{"name":"Department of Applied Chemistry, The University of Tokyo Graduate School of Engineering","place":["Tokyo, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takehiko","family":"Kitamori","sequence":"additional","affiliation":[{"name":"Department of Mechanical Engineering, The University of Tokyo Graduate School of Engineering","place":["Tokyo, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5519-172X","authenticated-orcid":true,"given":"Shinichi","family":"Sato","sequence":"additional","affiliation":[{"name":"Department of Dermatology, The University of Tokyo Graduate School of Medicine","place":["Tokyo, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4374","published-online":{"date-parts":[[2021,12,2]]},"reference":[{"key":"bib1","doi-asserted-by":"publisher","first-page":"581","DOI":"10.1002\/art.1780230510","article-title":"Preliminary criteria for the classification of systemic sclerosis (scleroderma). 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