AIRE expression controls the peripheral selection of autoreactive B cells.
Sci Immunol
; 4(34)2019 04 12.
Article
em En
| MEDLINE
| ID: mdl-30979797
ABSTRACT
Autoimmune regulator (AIRE) mutations result in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) syndrome characterized by defective central T cell tolerance and the production of many autoantibodies targeting tissue-specific antigens and cytokines. By studying CD3- and AIRE-deficient patients, we found that lack of either T cells or AIRE function resulted in the peripheral accumulation of autoreactive mature naïve B cells. Proteomic arrays and Biacore affinity measurements revealed that unmutated antibodies expressed by these autoreactive naïve B cells recognized soluble molecules and cytokines including insulin, IL-17A, and IL-17F, which are AIRE-dependent thymic peripheral tissue antigens targeted by autoimmune responses in APECED. AIRE-deficient patients also displayed decreased frequencies of regulatory T cells (Tregs) that lacked common TCRß clones found instead in their conventional T cell compartment, thereby suggesting holes in the Treg TCR repertoire of these patients. Hence, AIRE-mediated T cell/Treg selection normally prevents the expansion of autoreactive naïve B cells recognizing peripheral self-antigens.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Autoanticorpos
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Fatores de Transcrição
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Linfócitos B
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Autoimunidade
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Poliendocrinopatias Autoimunes
Tipo de estudo:
Observational_studies
Limite:
Adolescent
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Child
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Child, preschool
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Female
/
Humans
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Male
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Middle aged
Idioma:
En
Revista:
Sci Immunol
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Estados Unidos