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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
Arteriosclerosis, thrombosis, and vascular biology, 2016-April, 2016-Apr, 2016-04-00, 20160401, Letnik: 36, Številka: 4Journal Article
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) to identify B-cell functions involved in the metabolic consequences of obesity. APPROACH AND RESULTS—Diet-induced obese Id3 mice demonstrated attenuated inflammation and insulin resistance in visceral adipose tissue (VAT), and improved systemic glucose tolerance. VAT in Id3 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 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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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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in: SICRIS
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