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

• DOI: 10.1161/atvbaha.116.307166
• Publication Date: 2016-02-12T05:28:30Z
• Authors: 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
• Keywords: Blood Glucose; Homeodomain Proteins; Inflammation; Male; 2. Zero hunger; Genotype; Immunoglobulin mu-Chains; B-Lymphocyte Subsets; Intra-Abdominal Fat; Adoptive Transfer; Disease Models, Animal; 03 medical and health sciences; 0302 clinical medicine; Glucose Intolerance; Animals; Cytokines; Humans; Insulin; Inhibitor of Differentiation Proteins; Inflammation Mediators; Insulin Resistance; Biomarkers; Cells, Cultured

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 consequences obesity. Approach and Results— Diet-induced obese mice demonstrated attenuated inflammation insulin resistance visceral adipose tissue (VAT), improved systemic glucose tolerance. VAT had increased B-1b elevated IgM natural antibodies oxidation-specific epitopes. reduced cytokine production M1 macrophages, adoptively transferred trafficked produced for duration 13-week studies. null proliferation, established larger populations Rag1 −/− VAT, diet-induced intolerance hosts. However, transfer unable secrete no effect on In an human population, results provided first evidence that B-1 are enriched epitopes inversely correlated resistance. Conclusions— NAb-producing attenuate mice. Additional findings as reservoir link anti-inflammatory phenotype humans.