Abstract 205: Protective Role for B-1 B Cells and IgM Antibodies in Obesity
Innate B-1 B cells can protect against inflammatory disease through production of natural IgM antibodies, but little is known regarding their role in obesity-induced metabolic dysfunction. In this study, we explore the role murine B-1 B cells play in regulating diet-induced glucose intolerance. In addition, we examine bariatric surgery samples for the presence of B cells in human adipose tissue and circulating natural IgM antibodies.
We show that mice with increased visceral adipose tissue B-1b B cells due to B cell specific deletion of Id3 (Id3BcellKO) have attenuated high-fat diet-induced glucose intolerance compared to littermate controls. Omental visceral adipose tissue from Id3BcellKO mice had enhanced local natural IgM antibody secretion (49.0 ± 5.9 vs. 17.5 ± 4.2 U/mg fat), and demonstrated attenuated HFD-induced secretion of TNFa (2.5 ± 0.3 vs. 6.7 ± 1.3 pg/mg fat) and IFNg (0.10 ± 0.02 vs. 0.48 ± 0.14 pg/mg fat). Adoptive transfer of B-1b B cells null for Id3 protected against diet-induced glucose intolerance in Rag1-/- hosts, while B-1b B cells unable to secrete IgM had no effect. Additional studies in humans undergoing bariatric surgery showed CD20+CD27+CD43+ B cells, previously shown to have B-1-like characteristics, within omental adipose tissue. A correlation was found between their presence and serum natural IgM levels (r=0.52). In addition, natural IgM levels were inversely associated with the inflammatory chemokine, MCP-1 (r=-0.21). Finally, IgM, but not IgG, natural antibodies were inversely associated with insulin resistance (r=0.32).
Together, our findings provide the first evidence that B-1b B cells protect against diet-induced glucose intolerance in an IgM-dependent manner in mice, and suggest that anti-inflammatory natural IgM antibodies may modulate the inflammatory and metabolic consequences of obesity in humans.
Author Disclosures: D. Harmon: None. S.N. Oldham: None. C.C. McSkimming: None. H.M. Perry: None. J.L. Kirby: None. J.L. Kaplan: None. P. Hallowell: None. B. Schirmer: None. S. Tsimikas: None. A. Taylor: None. C. McNamara: None.
This research has received full or partial funding support from the American Heart Association.
- © 2014 by American Heart Association, Inc.