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Diabetes. 2015 Feb;64(2):593-603. doi: 10.2337/db14-0554. Epub 2014 Sep 23.

B-1a lymphocytes attenuate insulin resistance.

Author information

1
Shanghai Institute of Immunology, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
2
Department of Pathology, Stanford University School of Medicine, Stanford, CA.
3
Division of Cellular & Molecular Biology, Diabetes Research Group, Toronto General Research Institute (TGRI), University Health Network, Toronto, Ontario, Canada edengleman@stanford.edu dan.winer@uhn.ca.
4
Department of Pathology, Stanford University School of Medicine, Stanford, CA edengleman@stanford.edu dan.winer@uhn.ca.

Abstract

Obesity-associated insulin resistance, a common precursor of type 2 diabetes, is characterized by chronic inflammation of tissues, including visceral adipose tissue (VAT). Here we show that B-1a cells, a subpopulation of B lymphocytes, are novel and important regulators of this process. B-1a cells are reduced in frequency in obese high-fat diet (HFD)-fed mice, and EGFP interleukin-10 (IL-10) reporter mice show marked reductions in anti-inflammatory IL-10 production by B cells in vivo during obesity. In VAT, B-1a cells are the dominant producers of B cell-derived IL-10, contributing nearly half of the expressed IL-10 in vivo. Adoptive transfer of B-1a cells into HFD-fed B cell-deficient mice rapidly improves insulin resistance and glucose tolerance through IL-10 and polyclonal IgM-dependent mechanisms, whereas transfer of B-2 cells worsens metabolic disease. Genetic knockdown of B cell-activating factor (BAFF) in HFD-fed mice or treatment with a B-2 cell-depleting, B-1a cell-sparing anti-BAFF antibody attenuates insulin resistance. These findings establish B-1a cells as a new class of immune regulators that maintain metabolic homeostasis and suggest manipulation of these cells as a potential therapy for insulin resistance.

PMID:
25249575
PMCID:
PMC4303967
DOI:
10.2337/db14-0554
[Indexed for MEDLINE]
Free PMC Article

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