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

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 (Id3Bcell KO) to identify B-cell functions involved in the metabolic consequences of obesity. Approach and Results—Diet-induced obese Id3Bcell KO mice demonstrated attenuated inflammation and insulin resistance in visceral adipose tissue (VAT), and improved systemic glucose tolerance. VAT in Id3Bcell 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 ...