Adaptive tolerance: Protection through self-recognition.
B cells
IgD
IgM
autoantibodies
autoimmunity
tolerance
Journal
BioEssays : news and reviews in molecular, cellular and developmental biology
ISSN: 1521-1878
Titre abrégé: Bioessays
Pays: United States
ID NLM: 8510851
Informations de publication
Date de publication:
03 2022
03 2022
Historique:
revised:
11
12
2021
received:
07
10
2021
accepted:
17
12
2021
pubmed:
6
1
2022
medline:
6
5
2022
entrez:
5
1
2022
Statut:
ppublish
Résumé
The random nature of immunoglobulin gene segment rearrangement inevitably leads to the generation of self-reactive B cells. Avoidance of destructive autoimmune reactions is necessary in order to maintain physiological homeostasis. However, current central and peripheral tolerance concepts fail to explain the massive number of autoantibody-borne autoimmune diseases. Moreover, recent studies have shown that in physiological mouse models autoreactive B cells were neither clonally deleted nor kept in an anergic state, but were instead able to mount autoantibody responses. We propose that activation of autoreactive B cells is induced by polyvalent autoantigen complexes that can occur under physiological conditions. Repeated encounter of autoantigen complexes leads to the production of affinity-matured autoreactive IgM that protects its respective self-targets from degradation. We refer to this novel mechanism as adaptive tolerance. This article discusses the discovery of adaptive tolerance and the unexpected role of high affinity IgM autoantibodies.
Identifiants
pubmed: 34984705
doi: 10.1002/bies.202100236
doi:
Substances chimiques
Autoantibodies
0
Autoantigens
0
Immunoglobulin M
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e2100236Informations de copyright
© 2022 Wiley Periodicals LLC.
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