B Cells Promote Insulin Resistance Through Modulation of T Cells and Production of Pathogenic IgG Antibodies

Overview

Journal Nat Med

Specialties General Medicine
Molecular Biology

Date 2011 Apr 19

PMID 21499269

Citations 529

Authors

Daniel A 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 Glassford

Maria Caimol

Justin A Kenkel

Thomas F Tedder

Tracey McLaughlin

David B Miklos

H-Michael Dosch

Edgar G Engleman

Affiliations

Soon will be listed here.

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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