B Lymphocytes Promote Insulin Resistance through Modulation of T Lymphocytes and Production of Pathogenic IgG Antibody

By D. Winer, S. Winer, Lei Shen, Persis P. Wadia, J. Yantha, G. Paltser, Hubert Tsui, Ping Wu, Matthew G. Davidson, Michael N. Alonso and 9 more. Nature Medicine, 2011

1,008 citations recorded by the source corpus.

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.

Subfields: Epidemiology, Immunology

View Paper: https://www.semanticscholar.org/paper/55c0b836a0965d34dd44e1bbb3040aa99ed433e7

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Citations in the corpus

Adipokines Mediate Inflammation and Insulin Resistance (2013, background): “B cells produce IgG2c autoantibodies to induce systemic inflammation, and B cell deficient mice and depletion of B cells using anti-CD20 antibody administration suppress systemic inflammation and enhance insulin sensitivity (Winer et al., 2011).”
Chronic Adipose Tissue Inflammation Linking Obesity to Insulin Resistance and Type 2 Diabetes (2020, background): “Transfer of B cells from obese donor mice causes impaired insulin sensitivity and glucose homeostasis in the recipients (Winer et al., 2011; Hotamisligil, 2017).”
The ominous triad of adipose tissue dysfunction: inflammation, fibrosis, and impaired angiogenesis. (2017, positive): “In addition to cytokines, B2 cells also produce over a hundred different antibodies that have been associated with insulin resistance in human AT (8, 9).”
Adipose Tissue Distribution, Inflammation and Its Metabolic Consequences, Including Diabetes and Cardiovascular Disease (2020, background): “B-cells and mast cells also are increased in adipose tissue in the obese state (227, 236, 237).”