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- Title
B cells promote insulin resistance through modulation of T cells and production of pathogenic IgG antibodies.
- Authors
Winer, Daniel A; Winer, Shawn; Shen, Lei; Wadia, Persis P; Yantha, Jason; Paltser, Geoffrey; Tsui, Hubert; Wu, Ping; Davidson, Matthew G; Alonso, Michael N; Leong, Hwei X; Glassford, Alec; Caimol, Maria; Kenkel, Justin A; Tedder, Thomas F; McLaughlin, Tracey; Miklos, David B; Dosch, H-Michael; Engleman, Edgar G
- Abstract
Chronic inflammation characterized by T cell and macrophage infiltration of visceral adipose tissue (VAT) is a hallmark of obesity-associated insulin resistance and glucose intolerance. Here we show a fundamental pathogenic role for B cells in the development of these metabolic abnormalities. B cells accumulate in VAT in diet-induced obese (DIO) mice, and DIO mice lacking B cells are protected from disease despite weight gain. B cell effects on glucose metabolism are mechanistically linked to the activation of proinflammatory macrophages and T cells and to the production of pathogenic IgG antibodies. Treatment with a B cell-depleting CD20 antibody attenuates disease, whereas transfer of IgG from DIO mice rapidly induces insulin resistance and glucose intolerance. Moreover, insulin resistance in obese humans is associated with a unique profile of IgG autoantibodies. These results establish the importance of B cells and adaptive immunity in insulin resistance and suggest new diagnostic and therapeutic modalities for managing the disease.
- Publication
Nature medicine, 2011, Vol 17, Issue 5, p610
- ISSN
1546-170X
- Publication type
Journal Article
- DOI
10.1038/nm.2353