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

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

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 types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoantibodies / biosynthesis
  • Autoantigens / immunology
  • Autoimmunity
  • B-Lymphocytes / immunology*
  • Dietary Fats / adverse effects
  • Glucose / metabolism
  • Humans
  • Immunoglobulin G / biosynthesis*
  • Immunoglobulin mu-Chains / genetics
  • Inflammation / immunology
  • Insulin Resistance / immunology*
  • Intra-Abdominal Fat / immunology
  • Lymphocyte Activation
  • Lymphocyte Depletion
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Obesity / etiology
  • Obesity / immunology
  • Obesity / metabolism
  • T-Lymphocytes / immunology*

Substances

  • Autoantibodies
  • Autoantigens
  • Dietary Fats
  • Immunoglobulin G
  • Immunoglobulin mu-Chains
  • Glucose