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

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

Research output: Contribution to journalArticle

56 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1187-1198
Number of pages12
JournalCell Reports
Volume3
Issue number4
DOIs
StatePublished - Apr 25 2013

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Fingerprint Dive into the research topics of 'Obesity-Associated Autoantibody Production Requires AIM to Retain the Immunoglobulin M Immune Complex on Follicular Dendritic Cells'. Together they form a unique fingerprint.

  • Cite this

    Arai, S., Maehara, N., Iwamura, Y., Honda, S. I., Nakashima, K., Kai, T., Ogishi, M., Morita, K., Kurokawa, J., Mori, M., Motoi, Y., Miyake, K., Matsuhashi, N., Yamamura, K. I., Ohara, O., Shibuya, A., Wakeland, E. K., Li, Q. Z., & Miyazaki, T. (2013). Obesity-Associated Autoantibody Production Requires AIM to Retain the Immunoglobulin M Immune Complex on Follicular Dendritic Cells. Cell Reports, 3(4), 1187-1198. https://doi.org/10.1016/j.celrep.2013.03.006