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Nat Med. 2011 May;17(5):610-7. doi: 10.1038/nm.2353. Epub 2011 Apr 17.

B cells promote insulin resistance through modulation of T cells and production of pathogenic IgG antibodies.

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  • 1Department of Pathology, Stanford University, Palo Alto, California, USA. dan.winer@uhn.on.ca

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.

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PMID:
21499269
[PubMed - indexed for MEDLINE]
PMCID:
PMC3270885
Free PMC Article
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