An apoptosis-dependent checkpoint for autoimmunity in memory B and plasma cells.
Proc Natl Acad Sci U S A
; 117(40): 24957-24963, 2020 10 06.
Article
em En
| MEDLINE
| ID: mdl-32963096
ABSTRACT
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.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Genes de Imunoglobulinas
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Autoimunidade
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Apoptose
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Tolerância Imunológica
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article