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

Takemichi Fukasawa, Ayumi Yoshizaki, Satoshi Ebata, Asako Yoshizaki-Ogawa, Yoshihide Asano, Atsushi Enomoto, Kiyoshi Miyagawa, Yutaka Kazoe, Kazuma Mawatari, Takehiko Kitamori, Shinichi Sato

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article numbere67209
JournaleLife
Volume10
DOIs
Publication statusPublished - 2021 Dec

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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