IRAK-4- and MyD88-dependent pathways are essential for the removal of developing autoreactive B cells in humans.
Immunity
; 29(5): 746-57, 2008 Nov 14.
Article
en En
| MEDLINE
| ID: mdl-19006693
ABSTRACT
Most autoreactive B cells are normally counterselected during early B cell development. To determine whether Toll-like receptors (TLRs) regulate the removal of autoreactive B lymphocytes, we tested the reactivity of recombinant antibodies from single B cells isolated from patients deficient for interleukin-1 receptor-associated kinase 4 (IRAK-4), myeloid differentiation factor 88 (MyD88), and UNC-93B. Indeed, all TLRs except TLR3 require IRAK-4 and MyD88 to signal, and UNC-93B-deficient cells are unresponsive to TLR3, TLR7, TLR8, and TLR9. All patients suffered from defective central and peripheral B cell tolerance checkpoints, resulting in the accumulation of large numbers of autoreactive mature naive B cells in their blood. Hence, TLR7, TLR8, and TLR9 may prevent the recruitment of developing autoreactive B cells in healthy donors. Paradoxically, IRAK-4-, MyD88-, and UNC-93B-deficient patients did not display autoreactive antibodies in their serum or develop autoimmune diseases, suggesting that IRAK-4, MyD88, and UNC-93B pathway blockade may thwart autoimmunity in humans.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Proteínas de Transporte de Membrana
/
Linfocitos B
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Autoinmunidad
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Autotolerancia
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Receptores Toll-Like
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Quinasas Asociadas a Receptores de Interleucina-1
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Factor 88 de Diferenciación Mieloide
Límite:
Adult
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Child
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Female
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Humans
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Infant
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Male
Idioma:
En
Revista:
Immunity
Asunto de la revista:
ALERGIA E IMUNOLOGIA
Año:
2008
Tipo del documento:
Article
País de afiliación:
Estados Unidos