Abstract 80: Loss of Id3 in B Cells Leads to Increased Adipose Tissue T15-IgM and Protects Against Diet-Induced Glucose Intolerance
Background B1 B cells [[Unable to Display Character: –]] the major producers of anti-inflammatory natural T15-IgM antibodies that promote tissue homeostasis [[Unable to Display Character: –]] have been identified in adipose tissue, but their role in adipose tissue response to high-fat diet (HFD)-induced obesity is unclear. Our group and others have shown that the helix-loop-helix protein Id3 is a key regulator of B cell function in disease; mice null for Id3 have increased IgM levels and are protected from HFD-induced obesity. In this study, we test the hypothesis that B cell-specific Id3 deletion protects against the consequences of HFD-induced obesity through increased local production of natural IgM antibodies.
Methods and Results C57Bl/6 floxed Id3 (Id3fl/fl) and CD19cre/+ mice were crossed to create an Id3fl/fl CD19cre/+ mouse. While these mice had similar body and adipose depot mass as littermate controls after 12 weeks of HFD, they had significantly improved glucose clearance (2hr blood glucose: 314 ± 33 vs. 420 ± 38 mg/dl; n=7-11; p<0.05). At baseline, these mice were found to have significantly more B1b B cell than controls in the peritoneal fluid (3.2E5 ± 0.4E5 vs. 0.9E5 ± 0.4E5 cells; n=5-8; p<0.01), epididymal adipose tissue (4072 ± 923 vs. 1149 ± 652 cells/g fat; n=5-8; p<0.05), and omental adipose tissue. There were no differences in B1a or B2 cells in any compartment, and the mice had similar T cell and macrophage numbers in epididymal adipose tissue. ELISA analysis on whole epididymal adipose tissue revealed significantly higher levels of both total IgM (0.64 ± 0.06 vs. 0.24 ± 0.01 ng/ug protein; n=3-7; p<0.001) and T15-IgM (7.6 ± 1.5 vs. 2.8 ± 0.4 U/ng protein; n=3-7; p<0.05) in mice null for Id3 in B cells compared to controls. No differences were observed in the serum. In addition, omental fat from Id3fl/fl CD19cre/+ mice cultured ex vivo secreted significantly more T15-IgM than omental fat from littermate controls (40.0 ± 5.9 vs. 17.5 ± 4.2 U/mg fat; n=3-4; p<0.01).
Conclusions Loss of Id3 expression in B cells leads to elevated B1b B cells and increased local T15-IgM production in omental adipose tissue, along with improved glucose tolerance in mice fed a HFD, suggesting that T15-IgM may protect against the metabolic dysfunction caused by obesity.
- © 2013 by American Heart Association, Inc.