B cells promote insulin resistance through modulation of T cells and production of pathogenic IgG antibodies
Daniel A. Winer,Shawn Winer,Shawn Winer,Lei Shen,Persis P. Wadia,Jason Yantha,Geoffrey Paltser,Hubert Tsui,Ping Wu,Matthew G. Davidson,Michael N. Alonso,Hwei X Leong,Alec J. Glassford,Maria Caimol,Justin A. Kenkel,Thomas F. Tedder,Tracey McLaughlin,David B. Miklos,H.-M. Dosch,Edgar G. Engleman +19 more
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TLDR
The results establish the importance of B cells and adaptive immunity in insulin resistance and suggest new diagnostic and therapeutic modalities for managing the disease.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.read more
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