eLife (Dec 2021)

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

DOI
https://doi.org/10.7554/eLife.67209
Journal volume & issue
Vol. 10

Abstract

Read online

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.

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