Protective Role for B-1b B Cells and IgM in Obesity-Associated Inflammation, Glucose Intolerance, and Insulin Resistance

Daniel B. Harmon, Prasad Srikakulapu, Jennifer L. Kaplan, Stephanie N. Oldham, Chantel McSkimming, James C. Garmey, Heather M. Perry, Jennifer L. Kirby, Thomas A. Prohaska, Ayelet Gonen, Peter Hallowell, Bruce Schirmer, Sotirios Tsimikas, Angela M. Taylor, Joseph L. Witztum, Coleen A. McNamara

Research output: Contribution to journalArticle

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Abstract

Objective - Little is known about the role(s) B cells play in obesity-induced metabolic dysfunction. This study used a mouse with B-cell-specific deletion of Id3 (Id3 Bcell KO ) to identify B-cell functions involved in the metabolic consequences of obesity. Approach and Results - Diet-induced obese Id3 Bcell KO mice demonstrated attenuated inflammation and insulin resistance in visceral adipose tissue (VAT), and improved systemic glucose tolerance. VAT in Id3 Bcell KO mice had increased B-1b B cells and elevated IgM natural antibodies to oxidation-specific epitopes. B-1b B cells reduced cytokine production in VAT M1 macrophages, and adoptively transferred B-1b B cells trafficked to VAT and produced natural antibodies for the duration of 13-week studies. B-1b B cells null for Id3 demonstrated increased proliferation, established larger populations in Rag1 -/- VAT, and attenuated diet-induced glucose intolerance and VAT insulin resistance in Rag1 -/- hosts. However, transfer of B-1b B cells unable to secrete IgM had no effect on glucose tolerance. In an obese human population, results provided the first evidence that B-1 cells are enriched in human VAT and IgM antibodies to oxidation-specific epitopes inversely correlated with inflammation and insulin resistance. Conclusions - NAb-producing B-1b B cells are increased in Id3 Bcell KO mice and attenuate adipose tissue inflammation and glucose intolerance in diet-induced obese mice. Additional findings are the first to identify VAT as a reservoir for human B-1 cells and to link anti-inflammatory IgM antibodies with reduced inflammation and improved metabolic phenotype in obese humans.

Original languageEnglish (US)
Pages (from-to)682-691
Number of pages10
JournalArteriosclerosis, thrombosis, and vascular biology
Volume36
Issue number4
DOIs
StatePublished - Apr 1 2016

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Glucose Intolerance
Intra-Abdominal Fat
Immunoglobulin M
Insulin Resistance
B-Lymphocytes
Obesity
Inflammation
Antibodies
Diet
Epitopes
Glucose
Obese Mice
Population
Adipose Tissue
Anti-Inflammatory Agents
Macrophages
Cytokines
Phenotype

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

Cite this

Protective Role for B-1b B Cells and IgM in Obesity-Associated Inflammation, Glucose Intolerance, and Insulin Resistance. / Harmon, Daniel B.; Srikakulapu, Prasad; Kaplan, Jennifer L.; Oldham, Stephanie N.; McSkimming, Chantel; Garmey, James C.; Perry, Heather M.; Kirby, Jennifer L.; Prohaska, Thomas A.; Gonen, Ayelet; Hallowell, Peter; Schirmer, Bruce; Tsimikas, Sotirios; Taylor, Angela M.; Witztum, Joseph L.; McNamara, Coleen A.

In: Arteriosclerosis, thrombosis, and vascular biology, Vol. 36, No. 4, 01.04.2016, p. 682-691.

Research output: Contribution to journalArticle

Harmon, DB, Srikakulapu, P, Kaplan, JL, Oldham, SN, McSkimming, C, Garmey, JC, Perry, HM, Kirby, JL, Prohaska, TA, Gonen, A, Hallowell, P, Schirmer, B, Tsimikas, S, Taylor, AM, Witztum, JL & McNamara, CA 2016, 'Protective Role for B-1b B Cells and IgM in Obesity-Associated Inflammation, Glucose Intolerance, and Insulin Resistance', Arteriosclerosis, thrombosis, and vascular biology, vol. 36, no. 4, pp. 682-691. https://doi.org/10.1161/ATVBAHA.116.307166
Harmon, Daniel B. ; Srikakulapu, Prasad ; Kaplan, Jennifer L. ; Oldham, Stephanie N. ; McSkimming, Chantel ; Garmey, James C. ; Perry, Heather M. ; Kirby, Jennifer L. ; Prohaska, Thomas A. ; Gonen, Ayelet ; Hallowell, Peter ; Schirmer, Bruce ; Tsimikas, Sotirios ; Taylor, Angela M. ; Witztum, Joseph L. ; McNamara, Coleen A. / Protective Role for B-1b B Cells and IgM in Obesity-Associated Inflammation, Glucose Intolerance, and Insulin Resistance. In: Arteriosclerosis, thrombosis, and vascular biology. 2016 ; Vol. 36, No. 4. pp. 682-691.
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abstract = "Objective - Little is known about the role(s) B cells play in obesity-induced metabolic dysfunction. This study used a mouse with B-cell-specific deletion of Id3 (Id3 Bcell KO ) to identify B-cell functions involved in the metabolic consequences of obesity. Approach and Results - Diet-induced obese Id3 Bcell KO mice demonstrated attenuated inflammation and insulin resistance in visceral adipose tissue (VAT), and improved systemic glucose tolerance. VAT in Id3 Bcell KO mice had increased B-1b B cells and elevated IgM natural antibodies to oxidation-specific epitopes. B-1b B cells reduced cytokine production in VAT M1 macrophages, and adoptively transferred B-1b B cells trafficked to VAT and produced natural antibodies for the duration of 13-week studies. B-1b B cells null for Id3 demonstrated increased proliferation, established larger populations in Rag1 -/- VAT, and attenuated diet-induced glucose intolerance and VAT insulin resistance in Rag1 -/- hosts. However, transfer of B-1b B cells unable to secrete IgM had no effect on glucose tolerance. In an obese human population, results provided the first evidence that B-1 cells are enriched in human VAT and IgM antibodies to oxidation-specific epitopes inversely correlated with inflammation and insulin resistance. Conclusions - NAb-producing B-1b B cells are increased in Id3 Bcell KO mice and attenuate adipose tissue inflammation and glucose intolerance in diet-induced obese mice. Additional findings are the first to identify VAT as a reservoir for human B-1 cells and to link anti-inflammatory IgM antibodies with reduced inflammation and improved metabolic phenotype in obese humans.",
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AU - Harmon, Daniel B.

AU - Srikakulapu, Prasad

AU - Kaplan, Jennifer L.

AU - Oldham, Stephanie N.

AU - McSkimming, Chantel

AU - Garmey, James C.

AU - Perry, Heather M.

AU - Kirby, Jennifer L.

AU - Prohaska, Thomas A.

AU - Gonen, Ayelet

AU - Hallowell, Peter

AU - Schirmer, Bruce

AU - Tsimikas, Sotirios

AU - Taylor, Angela M.

AU - Witztum, Joseph L.

AU - McNamara, Coleen A.

PY - 2016/4/1

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N2 - Objective - Little is known about the role(s) B cells play in obesity-induced metabolic dysfunction. This study used a mouse with B-cell-specific deletion of Id3 (Id3 Bcell KO ) to identify B-cell functions involved in the metabolic consequences of obesity. Approach and Results - Diet-induced obese Id3 Bcell KO mice demonstrated attenuated inflammation and insulin resistance in visceral adipose tissue (VAT), and improved systemic glucose tolerance. VAT in Id3 Bcell KO mice had increased B-1b B cells and elevated IgM natural antibodies to oxidation-specific epitopes. B-1b B cells reduced cytokine production in VAT M1 macrophages, and adoptively transferred B-1b B cells trafficked to VAT and produced natural antibodies for the duration of 13-week studies. B-1b B cells null for Id3 demonstrated increased proliferation, established larger populations in Rag1 -/- VAT, and attenuated diet-induced glucose intolerance and VAT insulin resistance in Rag1 -/- hosts. However, transfer of B-1b B cells unable to secrete IgM had no effect on glucose tolerance. In an obese human population, results provided the first evidence that B-1 cells are enriched in human VAT and IgM antibodies to oxidation-specific epitopes inversely correlated with inflammation and insulin resistance. Conclusions - NAb-producing B-1b B cells are increased in Id3 Bcell KO mice and attenuate adipose tissue inflammation and glucose intolerance in diet-induced obese mice. Additional findings are the first to identify VAT as a reservoir for human B-1 cells and to link anti-inflammatory IgM antibodies with reduced inflammation and improved metabolic phenotype in obese humans.

AB - Objective - Little is known about the role(s) B cells play in obesity-induced metabolic dysfunction. This study used a mouse with B-cell-specific deletion of Id3 (Id3 Bcell KO ) to identify B-cell functions involved in the metabolic consequences of obesity. Approach and Results - Diet-induced obese Id3 Bcell KO mice demonstrated attenuated inflammation and insulin resistance in visceral adipose tissue (VAT), and improved systemic glucose tolerance. VAT in Id3 Bcell KO mice had increased B-1b B cells and elevated IgM natural antibodies to oxidation-specific epitopes. B-1b B cells reduced cytokine production in VAT M1 macrophages, and adoptively transferred B-1b B cells trafficked to VAT and produced natural antibodies for the duration of 13-week studies. B-1b B cells null for Id3 demonstrated increased proliferation, established larger populations in Rag1 -/- VAT, and attenuated diet-induced glucose intolerance and VAT insulin resistance in Rag1 -/- hosts. However, transfer of B-1b B cells unable to secrete IgM had no effect on glucose tolerance. In an obese human population, results provided the first evidence that B-1 cells are enriched in human VAT and IgM antibodies to oxidation-specific epitopes inversely correlated with inflammation and insulin resistance. Conclusions - NAb-producing B-1b B cells are increased in Id3 Bcell KO mice and attenuate adipose tissue inflammation and glucose intolerance in diet-induced obese mice. Additional findings are the first to identify VAT as a reservoir for human B-1 cells and to link anti-inflammatory IgM antibodies with reduced inflammation and improved metabolic phenotype in obese humans.

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