Single-cell-level protein analysis revealing the roles of autoantigen-reactive B lymphocytes in autoimmune disease and the murine model.
B cell
cytokine
fibrosis
human
immunology
inflammation
mouse
single cell analysis
systemic sclerosis
Journal
eLife
ISSN: 2050-084X
Titre abrégé: Elife
Pays: England
ID NLM: 101579614
Informations de publication
Date de publication:
02 12 2021
02 12 2021
Historique:
received:
03
02
2021
accepted:
21
11
2021
entrez:
2
12
2021
pubmed:
3
12
2021
medline:
15
12
2021
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 34854378
doi: 10.7554/eLife.67209
pii: 67209
pmc: PMC8639144
doi:
pii:
Substances chimiques
Autoantigens
0
Cytokines
0
DNA Topoisomerases, Type I
EC 5.99.1.2
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2021, Fukasawa et al.
Déclaration de conflit d'intérêts
TF, AY, SE, AY, YA, AE, KM, YK, KM, TK, SS No competing interests declared
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