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B Lymphocytes in obesity-related adipose tissue inflammation and insulin resistance

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Abstract

Obesity-related insulin resistance is a chronic inflammatory condition that often gives rise to type 2 diabetes (T2D). Much evidence supports a role for pro-inflammatory T cells and macrophages in promoting local inflammation in tissues such as visceral adipose tissue (VAT) leading to insulin resistance. More recently, B cells have emerged as an additional critical player in orchestrating these processes. B cells infiltrate VAT and display functional and phenotypic changes in response to diet-induced obesity. B cells contribute to insulin resistance by presenting antigens to T cells, secreting inflammatory cytokines, and producing pathogenic antibodies. B cell manipulation represents a novel approach to the treatment of obesity-related insulin resistance and potentially to the prevention of T2D. This review summarizes the roles of B cells in governing VAT inflammation and the mechanisms by which these cells contribute to altered glucose homeostasis in insulin resistance.

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Abbreviations

T2D:

Type 2 diabetes

VAT:

Visceral adipose tissues

FALC:

Fat-associated lymphoid cluster

oxLDL:

Oxidized low-density lipoprotein

CSR:

Class switch recombination

SHM:

Somatic hypermutation

HFD:

High-fat diet

BCR:

B cell receptor

CLS:

Crown-like structure

DIO:

Diet-induced obese

GOSR1:

Golgi SNAP receptor complex member 1

GFAP:

Glial fibrillary acidic protein

BAFF:

B-cell activating factor

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Acknowledgments

This work was supported in part by NIH grant 1R01DK096038 (EE), CIHR Grant 119414 (DW), and CDA grants, OG-3-12-3844 (DW) and CS-5-12-3886 (DW).

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Authors and Affiliations

  1. Department of Pathology, Toronto General Hospital, University Health Network, University of Toronto, Eaton Wing, 11E − 424A, 200 Elizabeth Street, Toronto, ON, M5G 2C4, Canada

    Daniel A. Winer & Shawn Winer

  2. Division of Cellular and Molecular Biology, Diabetes Research Group, Toronto General Research Institute (TGRI), University Health Network, University of Toronto, Toronto, ON, Canada

    Daniel A. Winer & Shawn Winer

  3. Department of Pathology, Stanford University School of Medicine, 3373 Hillview Avenue, Palo Alto, CA, 94304, USA

    Melissa H. Y. Chng, Lei Shen & Edgar G. Engleman

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  1. Daniel A. Winer
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  5. Edgar G. Engleman
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Correspondence to Edgar G. Engleman.

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Winer, D.A., Winer, S., Chng, M.H.Y. et al. B Lymphocytes in obesity-related adipose tissue inflammation and insulin resistance. Cell. Mol. Life Sci. 71, 1033–1043 (2014). https://doi.org/10.1007/s00018-013-1486-y

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