An apoptosis-dependent checkpoint for autoimmunity in memory B and plasma cells.
Animals
Antibodies, Antinuclear
/ immunology
Apoptosis
/ genetics
Autoantibodies
/ immunology
Autoimmunity
/ genetics
B-Lymphocytes
/ immunology
Genes, Immunoglobulin
/ genetics
Germinal Center
/ immunology
Humans
Immune Tolerance
/ genetics
Immunologic Memory
/ genetics
Mice
Plasma Cells
/ immunology
B lymphocytes
antinuclear antibodies
apoptosis
autoantibody
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876
Informations de publication
Date de publication:
06 10 2020
06 10 2020
Historique:
pubmed:
24
9
2020
medline:
25
11
2020
entrez:
23
9
2020
Statut:
ppublish
Résumé
B lymphocytes acquire self-reactivity as an unavoidable byproduct of antibody gene diversification in the bone marrow and in germinal centers (GCs). Autoreactive B cells emerging from the bone marrow are silenced in a series of well-defined checkpoints, but less is known about how self-reactivity that develops by somatic mutation in GCs is controlled. Here, we report the existence of an apoptosis-dependent tolerance checkpoint in post-GC B cells. Whereas defective GC B cell apoptosis has no measurable effect on autoantibody development, disruption of post-GC apoptosis results in accumulation of autoreactive memory B cells and plasma cells, antinuclear antibody production, and autoimmunity. The data presented shed light on mechanisms that regulate immune tolerance and the development of autoantibodies.
Identifiants
pubmed: 32963096
pii: 2015372117
doi: 10.1073/pnas.2015372117
pmc: PMC7547173
doi:
Substances chimiques
Antibodies, Antinuclear
0
Autoantibodies
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
24957-24963Subventions
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : NIAID NIH HHS
ID : R37 AI037526
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI144462
Pays : United States
Organisme : Howard Hughes Medical Institute
Pays : United States
Déclaration de conflit d'intérêts
The authors declare no competing interest.
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