Single-cell-level protein analysis revealing the roles of autoantigen-reactive B lymphocytes in autoimmune disease and the murine model
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 becaus...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2021-12-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/67209 |
| _version_ | 1797991956756824064 |
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| author | Takemichi Fukasawa Ayumi Yoshizaki Satoshi Ebata Asako Yoshizaki-Ogawa Yoshihide Asano Atsushi Enomoto Kiyoshi Miyagawa Yutaka Kazoe Kazuma Mawatari Takehiko Kitamori Shinichi Sato |
| author_facet | Takemichi Fukasawa Ayumi Yoshizaki Satoshi Ebata Asako Yoshizaki-Ogawa Yoshihide Asano Atsushi Enomoto Kiyoshi Miyagawa Yutaka Kazoe Kazuma Mawatari Takehiko Kitamori Shinichi Sato |
| author_sort | Takemichi Fukasawa |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-11T09:00:23Z |
| format | Article |
| id | doaj.art-41969bc1d4ab4eb0b5535a40e0a4f551 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-11T09:00:23Z |
| publishDate | 2021-12-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-41969bc1d4ab4eb0b5535a40e0a4f5512022-12-22T04:32:47ZengeLife Sciences Publications LtdeLife2050-084X2021-12-011010.7554/eLife.67209Single-cell-level protein analysis revealing the roles of autoantigen-reactive B lymphocytes in autoimmune disease and the murine modelTakemichi Fukasawa0https://orcid.org/0000-0002-6093-1881Ayumi Yoshizaki1https://orcid.org/0000-0002-8194-9140Satoshi Ebata2Asako Yoshizaki-Ogawa3Yoshihide Asano4Atsushi Enomoto5Kiyoshi Miyagawa6Yutaka Kazoe7Kazuma Mawatari8Takehiko Kitamori9Shinichi Sato10https://orcid.org/0000-0001-5519-172XDepartment of Dermatology, The University of Tokyo Graduate School of Medicine, Tokyo, JapanDepartment of Dermatology, The University of Tokyo Graduate School of Medicine, Tokyo, JapanDepartment of Dermatology, The University of Tokyo Graduate School of Medicine, Tokyo, JapanDepartment of Dermatology, The University of Tokyo Graduate School of Medicine, Tokyo, JapanDepartment of Dermatology, The University of Tokyo Graduate School of Medicine, Tokyo, JapanLaboratory of Radiology and Biomedical Engineering, The University of Tokyo Graduate School of Medicine, Tokyo, JapanLaboratory of Radiology and Biomedical Engineering, The University of Tokyo Graduate School of Medicine, Tokyo, JapanDepartment of System Design Engineering, Keio university, Faculty of Science and technology, Tokyo, JapanDepartment of Applied Chemistry, The University of Tokyo Graduate School of Engineering, Tokyo, JapanDepartment of Mechanical Engineering, The University of Tokyo Graduate School of Engineering, Tokyo, JapanDepartment of Dermatology, The University of Tokyo Graduate School of Medicine, Tokyo, JapanDespite 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.https://elifesciences.org/articles/67209B cellsystemic sclerosisfibrosissingle cell analysiscytokine |
| spellingShingle | Takemichi Fukasawa Ayumi Yoshizaki Satoshi Ebata Asako Yoshizaki-Ogawa Yoshihide Asano Atsushi Enomoto Kiyoshi Miyagawa Yutaka Kazoe Kazuma Mawatari Takehiko Kitamori Shinichi Sato Single-cell-level protein analysis revealing the roles of autoantigen-reactive B lymphocytes in autoimmune disease and the murine model eLife B cell systemic sclerosis fibrosis single cell analysis cytokine |
| title | Single-cell-level protein analysis revealing the roles of autoantigen-reactive B lymphocytes in autoimmune disease and the murine model |
| title_full | Single-cell-level protein analysis revealing the roles of autoantigen-reactive B lymphocytes in autoimmune disease and the murine model |
| title_fullStr | Single-cell-level protein analysis revealing the roles of autoantigen-reactive B lymphocytes in autoimmune disease and the murine model |
| title_full_unstemmed | Single-cell-level protein analysis revealing the roles of autoantigen-reactive B lymphocytes in autoimmune disease and the murine model |
| title_short | Single-cell-level protein analysis revealing the roles of autoantigen-reactive B lymphocytes in autoimmune disease and the murine model |
| title_sort | single cell level protein analysis revealing the roles of autoantigen reactive b lymphocytes in autoimmune disease and the murine model |
| topic | B cell systemic sclerosis fibrosis single cell analysis cytokine |
| url | https://elifesciences.org/articles/67209 |
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