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

Autor:	Harmon DB; From the Cardiovascular Research Center (D.B.H., P.S., J.L.K., S.N.O., C.M.S., J.C.G., H.M.P., C.A.M.), Department of Biochemistry, Molecular Biology, and Genetics (D.B.H.), Division of Cardiovascular Medicine, Department of Medicine (P.S., A.M.T., C.A.M.), Department of Pathology (J.L.K., H.M.P.), Division of Endocrinology and Metabolism, Department of Medicine (J.L.K.), Department of Surgery (P.H., B.S.), Beirne B. Carter Center for Immunology Research (C.A.M.), Department of Molecular Physiology and Biological Physics (C.A.M.), University of Virginia, Charlottesville; and Department of Medicine, University of California San Diego, La Jolla (T.A.P., A.G., S.T., J.L.W.)., Srikakulapu P; From the Cardiovascular Research Center (D.B.H., P.S., J.L.K., S.N.O., C.M.S., J.C.G., H.M.P., C.A.M.), Department of Biochemistry, Molecular Biology, and Genetics (D.B.H.), Division of Cardiovascular Medicine, Department of Medicine (P.S., A.M.T., C.A.M.), Department of Pathology (J.L.K., H.M.P.), Division of Endocrinology and Metabolism, Department of Medicine (J.L.K.), Department of Surgery (P.H., B.S.), Beirne B. Carter Center for Immunology Research (C.A.M.), Department of Molecular Physiology and Biological Physics (C.A.M.), University of Virginia, Charlottesville; and Department of Medicine, University of California San Diego, La Jolla (T.A.P., A.G., S.T., J.L.W.)., Kaplan JL; From the Cardiovascular Research Center (D.B.H., P.S., J.L.K., S.N.O., C.M.S., J.C.G., H.M.P., C.A.M.), Department of Biochemistry, Molecular Biology, and Genetics (D.B.H.), Division of Cardiovascular Medicine, Department of Medicine (P.S., A.M.T., C.A.M.), Department of Pathology (J.L.K., H.M.P.), Division of Endocrinology and Metabolism, Department of Medicine (J.L.K.), Department of Surgery (P.H., B.S.), Beirne B. Carter Center for Immunology Research (C.A.M.), Department of Molecular Physiology and Biological Physics (C.A.M.), University of Virginia, Charlottesville; and Department of Medicine, University of California San Diego, La Jolla (T.A.P., A.G., S.T., J.L.W.)., Oldham SN; From the Cardiovascular Research Center (D.B.H., P.S., J.L.K., S.N.O., C.M.S., J.C.G., H.M.P., C.A.M.), Department of Biochemistry, Molecular Biology, and Genetics (D.B.H.), Division of Cardiovascular Medicine, Department of Medicine (P.S., A.M.T., C.A.M.), Department of Pathology (J.L.K., H.M.P.), Division of Endocrinology and Metabolism, Department of Medicine (J.L.K.), Department of Surgery (P.H., B.S.), Beirne B. Carter Center for Immunology Research (C.A.M.), Department of Molecular Physiology and Biological Physics (C.A.M.), University of Virginia, Charlottesville; and Department of Medicine, University of California San Diego, La Jolla (T.A.P., A.G., S.T., J.L.W.)., McSkimming C; From the Cardiovascular Research Center (D.B.H., P.S., J.L.K., S.N.O., C.M.S., J.C.G., H.M.P., C.A.M.), Department of Biochemistry, Molecular Biology, and Genetics (D.B.H.), Division of Cardiovascular Medicine, Department of Medicine (P.S., A.M.T., C.A.M.), Department of Pathology (J.L.K., H.M.P.), Division of Endocrinology and Metabolism, Department of Medicine (J.L.K.), Department of Surgery (P.H., B.S.), Beirne B. Carter Center for Immunology Research (C.A.M.), Department of Molecular Physiology and Biological Physics (C.A.M.), University of Virginia, Charlottesville; and Department of Medicine, University of California San Diego, La Jolla (T.A.P., A.G., S.T., J.L.W.)., Garmey JC; From the Cardiovascular Research Center (D.B.H., P.S., J.L.K., S.N.O., C.M.S., J.C.G., H.M.P., C.A.M.), Department of Biochemistry, Molecular Biology, and Genetics (D.B.H.), Division of Cardiovascular Medicine, Department of Medicine (P.S., A.M.T., C.A.M.), Department of Pathology (J.L.K., H.M.P.), Division of Endocrinology and Metabolism, Department of Medicine (J.L.K.), Department of Surgery (P.H., B.S.), Beirne B. Carter Center for Immunology Research (C.A.M.), Department of Molecular Physiology and Biological Physics (C.A.M.), University of Virginia, Charlottesville; and Department of Medicine, University of California San Diego, La Jolla (T.A.P., A.G., S.T., J.L.W.)., Perry HM; From the Cardiovascular Research Center (D.B.H., P.S., J.L.K., S.N.O., C.M.S., J.C.G., H.M.P., C.A.M.), Department of Biochemistry, Molecular Biology, and Genetics (D.B.H.), Division of Cardiovascular Medicine, Department of Medicine (P.S., A.M.T., C.A.M.), Department of Pathology (J.L.K., H.M.P.), Division of Endocrinology and Metabolism, Department of Medicine (J.L.K.), Department of Surgery (P.H., B.S.), Beirne B. Carter Center for Immunology Research (C.A.M.), Department of Molecular Physiology and Biological Physics (C.A.M.), University of Virginia, Charlottesville; and Department of Medicine, University of California San Diego, La Jolla (T.A.P., A.G., S.T., J.L.W.)., Kirby JL; From the Cardiovascular Research Center (D.B.H., P.S., J.L.K., S.N.O., C.M.S., J.C.G., H.M.P., C.A.M.), Department of Biochemistry, Molecular Biology, and Genetics (D.B.H.), Division of Cardiovascular Medicine, Department of Medicine (P.S., A.M.T., C.A.M.), Department of Pathology (J.L.K., H.M.P.), Division of Endocrinology and Metabolism, Department of Medicine (J.L.K.), Department of Surgery (P.H., B.S.), Beirne B. Carter Center for Immunology Research (C.A.M.), Department of Molecular Physiology and Biological Physics (C.A.M.), University of Virginia, Charlottesville; and Department of Medicine, University of California San Diego, La Jolla (T.A.P., A.G., S.T., J.L.W.)., Prohaska TA; From the Cardiovascular Research Center (D.B.H., P.S., J.L.K., S.N.O., C.M.S., J.C.G., H.M.P., C.A.M.), Department of Biochemistry, Molecular Biology, and Genetics (D.B.H.), Division of Cardiovascular Medicine, Department of Medicine (P.S., A.M.T., C.A.M.), Department of Pathology (J.L.K., H.M.P.), Division of Endocrinology and Metabolism, Department of Medicine (J.L.K.), Department of Surgery (P.H., B.S.), Beirne B. Carter Center for Immunology Research (C.A.M.), Department of Molecular Physiology and Biological Physics (C.A.M.), University of Virginia, Charlottesville; and Department of Medicine, University of California San Diego, La Jolla (T.A.P., A.G., S.T., J.L.W.)., Gonen A; From the Cardiovascular Research Center (D.B.H., P.S., J.L.K., S.N.O., C.M.S., J.C.G., H.M.P., C.A.M.), Department of Biochemistry, Molecular Biology, and Genetics (D.B.H.), Division of Cardiovascular Medicine, Department of Medicine (P.S., A.M.T., C.A.M.), Department of Pathology (J.L.K., H.M.P.), Division of Endocrinology and Metabolism, Department of Medicine (J.L.K.), Department of Surgery (P.H., B.S.), Beirne B. Carter Center for Immunology Research (C.A.M.), Department of Molecular Physiology and Biological Physics (C.A.M.), University of Virginia, Charlottesville; and Department of Medicine, University of California San Diego, La Jolla (T.A.P., A.G., S.T., J.L.W.)., Hallowell P; From the Cardiovascular Research Center (D.B.H., P.S., J.L.K., S.N.O., C.M.S., J.C.G., H.M.P., C.A.M.), Department of Biochemistry, Molecular Biology, and Genetics (D.B.H.), Division of Cardiovascular Medicine, Department of Medicine (P.S., A.M.T., C.A.M.), Department of Pathology (J.L.K., H.M.P.), Division of Endocrinology and Metabolism, Department of Medicine (J.L.K.), Department of Surgery (P.H., B.S.), Beirne B. Carter Center for Immunology Research (C.A.M.), Department of Molecular Physiology and Biological Physics (C.A.M.), University of Virginia, Charlottesville; and Department of Medicine, University of California San Diego, La Jolla (T.A.P., A.G., S.T., J.L.W.)., Schirmer B; From the Cardiovascular Research Center (D.B.H., P.S., J.L.K., S.N.O., C.M.S., J.C.G., H.M.P., C.A.M.), Department of Biochemistry, Molecular Biology, and Genetics (D.B.H.), Division of Cardiovascular Medicine, Department of Medicine (P.S., A.M.T., C.A.M.), Department of Pathology (J.L.K., H.M.P.), Division of Endocrinology and Metabolism, Department of Medicine (J.L.K.), Department of Surgery (P.H., B.S.), Beirne B. Carter Center for Immunology Research (C.A.M.), Department of Molecular Physiology and Biological Physics (C.A.M.), University of Virginia, Charlottesville; and Department of Medicine, University of California San Diego, La Jolla (T.A.P., A.G., S.T., J.L.W.)., Tsimikas S; From the Cardiovascular Research Center (D.B.H., P.S., J.L.K., S.N.O., C.M.S., J.C.G., H.M.P., C.A.M.), Department of Biochemistry, Molecular Biology, and Genetics (D.B.H.), Division of Cardiovascular Medicine, Department of Medicine (P.S., A.M.T., C.A.M.), Department of Pathology (J.L.K., H.M.P.), Division of Endocrinology and Metabolism, Department of Medicine (J.L.K.), Department of Surgery (P.H., B.S.), Beirne B. Carter Center for Immunology Research (C.A.M.), Department of Molecular Physiology and Biological Physics (C.A.M.), University of Virginia, Charlottesville; and Department of Medicine, University of California San Diego, La Jolla (T.A.P., A.G., S.T., J.L.W.)., Taylor AM; From the Cardiovascular Research Center (D.B.H., P.S., J.L.K., S.N.O., C.M.S., J.C.G., H.M.P., C.A.M.), Department of Biochemistry, Molecular Biology, and Genetics (D.B.H.), Division of Cardiovascular Medicine, Department of Medicine (P.S., A.M.T., C.A.M.), Department of Pathology (J.L.K., H.M.P.), Division of Endocrinology and Metabolism, Department of Medicine (J.L.K.), Department of Surgery (P.H., B.S.), Beirne B. Carter Center for Immunology Research (C.A.M.), Department of Molecular Physiology and Biological Physics (C.A.M.), University of Virginia, Charlottesville; and Department of Medicine, University of California San Diego, La Jolla (T.A.P., A.G., S.T., J.L.W.)., Witztum JL; From the Cardiovascular Research Center (D.B.H., P.S., J.L.K., S.N.O., C.M.S., J.C.G., H.M.P., C.A.M.), Department of Biochemistry, Molecular Biology, and Genetics (D.B.H.), Division of Cardiovascular Medicine, Department of Medicine (P.S., A.M.T., C.A.M.), Department of Pathology (J.L.K., H.M.P.), Division of Endocrinology and Metabolism, Department of Medicine (J.L.K.), Department of Surgery (P.H., B.S.), Beirne B. Carter Center for Immunology Research (C.A.M.), Department of Molecular Physiology and Biological Physics (C.A.M.), University of Virginia, Charlottesville; and Department of Medicine, University of California San Diego, La Jolla (T.A.P., A.G., S.T., J.L.W.)., McNamara CA; From the Cardiovascular Research Center (D.B.H., P.S., J.L.K., S.N.O., C.M.S., J.C.G., H.M.P., C.A.M.), Department of Biochemistry, Molecular Biology, and Genetics (D.B.H.), Division of Cardiovascular Medicine, Department of Medicine (P.S., A.M.T., C.A.M.), Department of Pathology (J.L.K., H.M.P.), Division of Endocrinology and Metabolism, Department of Medicine (J.L.K.), Department of Surgery (P.H., B.S.), Beirne B. Carter Center for Immunology Research (C.A.M.), Department of Molecular Physiology and Biological Physics (C.A.M.), University of Virginia, Charlottesville; and Department of Medicine, University of California San Diego, La Jolla (T.A.P., A.G., S.T., J.L.W.). cam8c@virginia.edu.
Jazyk:	angličtina
Zdroj:	Arteriosclerosis, thrombosis, and vascular biology [Arterioscler Thromb Vasc Biol] 2016 Apr; Vol. 36 (4), pp. 682-91. Date of Electronic Publication: 2016 Feb 11.
DOI:	10.1161/ATVBAHA.116.307166
Abstrakt:	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. (© 2016 American Heart Association, Inc.)
Databáze:	MEDLINE
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