Obesity-associated autoantibody production requires AIM to retain the immunoglobulin M immune complex on follicular dendritic cells.
Cell Rep
; 3(4): 1187-98, 2013 Apr 25.
Article
en En
| MEDLINE
| ID: mdl-23562157
ABSTRACT
Natural immunoglobulin M (IgM) is reactive to autoantigens and is believed to be important for autoimmunity. Blood pentameric IgM loaded with antigens forms a large immune complex (IC) that contains various elements, including apoptosis inhibitor of macrophage (AIM). Here we demonstrate that this IgM-AIM association contributes to autoantibody production under obese conditions. In mice fed a high-fat diet, natural IgM increased through B cell TLR4 stimulation. AIM associated with IgM and protected AIM from renal excretion, increasing blood AIM levels along with the obesity-induced IgM augmentation. Meanwhile, the AIM association inhibited IgM binding to the Fcα/µ receptor on splenic follicular dendritic cells, thereby protecting the IgM IC from Fcα/µ receptor-mediated internalization. This supported IgM-dependent autoantigen presentation to B cells, stimulating IgG autoantibody production. Accordingly, in obese AIM-deficient (AIM(-/-)) mice, the increase of multiple IgG autoantibodies observed in obese wild-type mice was abrogated. Thus, the AIM-IgM association plays a critical role in the obesity-associated autoimmune process.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Autoanticuerpos
/
Inmunoglobulina M
/
Receptores Inmunológicos
/
Células Dendríticas Foliculares
/
Proteínas Reguladoras de la Apoptosis
Tipo de estudio:
Risk_factors_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Cell Rep
Año:
2013
Tipo del documento:
Article
País de afiliación:
Japón