Inositol polyphosphates promote T cell-independent humoral immunity via the regulation of Bruton's tyrosine kinase.
Proc Natl Acad Sci U S A
; 116(26): 12952-12957, 2019 06 25.
Article
en En
| MEDLINE
| ID: mdl-31189594
ABSTRACT
T cell-independent (TI) B cell response is critical for the early protection against pathogen invasion. The regulation and activation of Bruton's tyrosine kinase (Btk) is known as a pivotal step of B cell antigen receptor (BCR) signaling in TI humoral immunity, as observed in patients with X-linked agammaglobulinemia (XLA) experiencing a high incidence of encapsulated bacterial infections. However, key questions remain as to whether a well-established canonical BCR signaling pathway is sufficient to regulate the activity of Btk. Here, we find that inositol hexakisphosphate (InsP6) acts as a physiological regulator of Btk in BCR signaling. Absence of higher order inositol phosphates (InsPs), inositol polyphosphates, leads to an inability to mount immune response against TI antigens. Interestingly, the significance of InsP6-mediated Btk regulation is more prominent in IgM+ plasma cells. Hence, the present study identifies higher order InsPs as principal components of B cell activation upon TI antigen stimulation and presents a mechanism for InsP-mediated regulation of the BCR signaling.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Asunto principal:
Ácido Fítico
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Fosfotransferasas (Aceptor de Grupo Alcohol)
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Agammaglobulinemia
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Enfermedades Genéticas Ligadas al Cromosoma X
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Inmunidad Humoral
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Agammaglobulinemia Tirosina Quinasa
Límite:
Animals
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Humans
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Año:
2019
Tipo del documento:
Article