Obesity-Associated Autoantibody Production Requires AIM to Retain the Immunoglobulin M Immune Complex on Follicular Dendritic Cells

作者：Satoko Arai, Natsumi Maehara, Yoshihiro Iwamura, Shin-ichiro Honda, Katsuhiko Nakashima, Toshihiro Kai, Masato Ogishi, Kumiko Morita, Jun Kurokawa, Mayumi Mori, Yuji Motoi, Kensuke Miyake, Nobuyuki Matsuhashi, Ken–ichi Yamamura, Osamu Ohara, Akira Shibuya, Edward K. Wakeland, Quan‐Zhen Li, Toru Miyazaki · 发表于：Cell Reports · 年份：2013 · DOI：10.1016/j.celrep.2013.03.006 · 被引用次数：118 · 研究领域：Immune Cell Function and Interaction、T-cell and B-cell Immunology、Diabetes and associated disorders

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.