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...
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2021
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oai:doaj.org-article:41969bc1d4ab4eb0b5535a40e0a4f5512021-12-02T10:23:44ZSingle-cell-level protein analysis revealing the roles of autoantigen-reactive B lymphocytes in autoimmune disease and the murine model10.7554/eLife.672092050-084Xe67209https://doaj.org/article/41969bc1d4ab4eb0b5535a40e0a4f5512021-12-01T00:00:00Zhttps://elifesciences.org/articles/67209https://doaj.org/toc/2050-084XDespite 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.Takemichi FukasawaAyumi YoshizakiSatoshi EbataAsako Yoshizaki-OgawaYoshihide AsanoAtsushi EnomotoKiyoshi MiyagawaYutaka KazoeKazuma MawatariTakehiko KitamoriShinichi SatoeLife Sciences Publications LtdarticleB cellsystemic sclerosisfibrosissingle cell analysiscytokineMedicineRScienceQBiology (General)QH301-705.5ENeLife, Vol 10 (2021) |
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B cell systemic sclerosis fibrosis single cell analysis cytokine Medicine R Science Q Biology (General) QH301-705.5 |
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B cell systemic sclerosis fibrosis single cell analysis cytokine Medicine R Science Q Biology (General) QH301-705.5 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 |
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. |
format |
article |
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 |
title |
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_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_sort |
single-cell-level protein analysis revealing the roles of autoantigen-reactive b lymphocytes in autoimmune disease and the murine model |
publisher |
eLife Sciences Publications Ltd |
publishDate |
2021 |
url |
https://doaj.org/article/41969bc1d4ab4eb0b5535a40e0a4f551 |
work_keys_str_mv |
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