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B lymphocytes as emerging mediators of insulin resistance.

Winer DA, Winer S, Shen L, Chng MH, Engleman EG - Int J Obes Suppl (2012)

Bottom Line: Obesity is associated with chronic inflammation of various tissues including visceral adipose tissue (VAT), which contributes to insulin resistance.T cells and macrophages infiltrate VAT in obesity and orchestrate this inflammation.Recently, we made the surprising discovery that B cells are important contributors to this process.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, University Health Network, University of Toronto , Toronto, Ontario, Canada ; Division of Cellular and Molecular Biology, Diabetes Research Group, Toronto General Research Institute (TGRI), University Health Network, University of Toronto , Toronto, Ontario, Canada.

ABSTRACT
Obesity is associated with chronic inflammation of various tissues including visceral adipose tissue (VAT), which contributes to insulin resistance. T cells and macrophages infiltrate VAT in obesity and orchestrate this inflammation. Recently, we made the surprising discovery that B cells are important contributors to this process. Thus, some B cells and the antibodies they produce can promote VAT-associated and systemic inflammation, leading to insulin resistance. This report will focus on the properties of these B cells, and how they contribute to insulin resistance through T-cell modulation and production of pathogenic autoantibodies. Understanding the mechanisms by which B cells contribute to insulin resistance should lead to new antibody-based diagnostics and B-cell modulating therapeutics to manage this increasingly prevalent disease.

No MeSH data available.


Related in: MedlinePlus

The role of B cells in VAT inflammation and insulin resistance. In the lean state, B cells produce IL-10, which promotes M2 macrophage polarization and insulin sensitivity. During obesity, B cells present insulin-resistance-associated antigens to T cells, leading to IFNγ production and M1 macrophage polarization. B cells undergo class switching to produce IgG2c with the potential to bind FcRs on macrophages and induce TNFα secretion. B cells also secrete pro-inflammatory chemokines such as IL-8, which may help recruit additional immune cells, including macrophages, to perpetuate the inflammation.
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fig1: The role of B cells in VAT inflammation and insulin resistance. In the lean state, B cells produce IL-10, which promotes M2 macrophage polarization and insulin sensitivity. During obesity, B cells present insulin-resistance-associated antigens to T cells, leading to IFNγ production and M1 macrophage polarization. B cells undergo class switching to produce IgG2c with the potential to bind FcRs on macrophages and induce TNFα secretion. B cells also secrete pro-inflammatory chemokines such as IL-8, which may help recruit additional immune cells, including macrophages, to perpetuate the inflammation.

Mentions: Our findings support a model in which B cells infiltrate VAT in obese individuals and associate with T cells and macrophages in CLS. B cells sample antigen from the surrounding tissues, possibly from dead adipocytes, and present peptides to VAT-associated CD4+ and CD8+ T cells, which produce IFNγ. In the presence of decreasing amounts of B-cell-derived IL-10, IFNγ polarizes nearby macrophages to an activated M1 phenotype. These M1 macrophages secrete large amounts of TNFα that acts in concert with IFNγ to cause insulin resistance. IL-8, produced by B cells, attracts additional inflammatory cells, including macrophages, to the site of VAT inflammation.47 B-cell-derived pathogenic IgG, including IgG2c, acts locally on macrophages in an Fc-dependent mechanism to further bolster TNFα production. IgG antibodies are also induced in spleens during obesity and may contribute systemically to insulin resistance in other target tissues. Figure 1 summarizes the roles of B cells in governing insulin resistance.


B lymphocytes as emerging mediators of insulin resistance.

Winer DA, Winer S, Shen L, Chng MH, Engleman EG - Int J Obes Suppl (2012)

The role of B cells in VAT inflammation and insulin resistance. In the lean state, B cells produce IL-10, which promotes M2 macrophage polarization and insulin sensitivity. During obesity, B cells present insulin-resistance-associated antigens to T cells, leading to IFNγ production and M1 macrophage polarization. B cells undergo class switching to produce IgG2c with the potential to bind FcRs on macrophages and induce TNFα secretion. B cells also secrete pro-inflammatory chemokines such as IL-8, which may help recruit additional immune cells, including macrophages, to perpetuate the inflammation.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4109086&req=5

fig1: The role of B cells in VAT inflammation and insulin resistance. In the lean state, B cells produce IL-10, which promotes M2 macrophage polarization and insulin sensitivity. During obesity, B cells present insulin-resistance-associated antigens to T cells, leading to IFNγ production and M1 macrophage polarization. B cells undergo class switching to produce IgG2c with the potential to bind FcRs on macrophages and induce TNFα secretion. B cells also secrete pro-inflammatory chemokines such as IL-8, which may help recruit additional immune cells, including macrophages, to perpetuate the inflammation.
Mentions: Our findings support a model in which B cells infiltrate VAT in obese individuals and associate with T cells and macrophages in CLS. B cells sample antigen from the surrounding tissues, possibly from dead adipocytes, and present peptides to VAT-associated CD4+ and CD8+ T cells, which produce IFNγ. In the presence of decreasing amounts of B-cell-derived IL-10, IFNγ polarizes nearby macrophages to an activated M1 phenotype. These M1 macrophages secrete large amounts of TNFα that acts in concert with IFNγ to cause insulin resistance. IL-8, produced by B cells, attracts additional inflammatory cells, including macrophages, to the site of VAT inflammation.47 B-cell-derived pathogenic IgG, including IgG2c, acts locally on macrophages in an Fc-dependent mechanism to further bolster TNFα production. IgG antibodies are also induced in spleens during obesity and may contribute systemically to insulin resistance in other target tissues. Figure 1 summarizes the roles of B cells in governing insulin resistance.

Bottom Line: Obesity is associated with chronic inflammation of various tissues including visceral adipose tissue (VAT), which contributes to insulin resistance.T cells and macrophages infiltrate VAT in obesity and orchestrate this inflammation.Recently, we made the surprising discovery that B cells are important contributors to this process.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, University Health Network, University of Toronto , Toronto, Ontario, Canada ; Division of Cellular and Molecular Biology, Diabetes Research Group, Toronto General Research Institute (TGRI), University Health Network, University of Toronto , Toronto, Ontario, Canada.

ABSTRACT
Obesity is associated with chronic inflammation of various tissues including visceral adipose tissue (VAT), which contributes to insulin resistance. T cells and macrophages infiltrate VAT in obesity and orchestrate this inflammation. Recently, we made the surprising discovery that B cells are important contributors to this process. Thus, some B cells and the antibodies they produce can promote VAT-associated and systemic inflammation, leading to insulin resistance. This report will focus on the properties of these B cells, and how they contribute to insulin resistance through T-cell modulation and production of pathogenic autoantibodies. Understanding the mechanisms by which B cells contribute to insulin resistance should lead to new antibody-based diagnostics and B-cell modulating therapeutics to manage this increasingly prevalent disease.

No MeSH data available.


Related in: MedlinePlus