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

DA Winer, S Winer, L Shen, PP Wadia, J Yantha… - Nature medicine, 2011 - nature.com
DA Winer, S Winer, L Shen, PP Wadia, J Yantha, G Paltser, H Tsui, P Wu, MG Davidson
Nature medicine, 2011nature.com
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 …
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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