| First Author | Arai S | Year | 2013 |
| Journal | Cell Rep | Volume | 3 |
| Issue | 4 | Pages | 1187-98 |
| PubMed ID | 23562157 | Mgi Jnum | J:198540 |
| Mgi Id | MGI:5496985 | Doi | 10.1016/j.celrep.2013.03.006 |
| Citation | Arai S, et al. (2013) Obesity-associated autoantibody production requires AIM to retain the immunoglobulin M immune complex on follicular dendritic cells. Cell Rep 3(4):1187-98 |
| abstractText | 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 Fcalpha/mu receptor on splenic follicular dendritic cells, thereby protecting the IgM IC from Fcalpha/mu 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. |
