Abstract 60: B Cell--Specific Deletion of Id3 is Atheroprotective and Enhances B1b B Cell Numbers and Antibody Production
Introduction: B cells have been shown to have subset specific functions in atherosclerosis. B1a B cells, which contribute to innate immunity, are atheroprotective due to the spontaneous generation of protective natural antibodies. B1b B cells, the sister population to B1a B cells, also produce natural antibodies and unlike B1a B cells, have memory and inducible properties. B1b B cells have not been studied in atherosclerosis. Our lab has demonstrated that the helix-loop-helix transcription factor Id3 is important for B cell mediated atheroprotection. However, how Id3 in B cells regulates atheroprotection is incompletely understood.
Hypothesis: Loss of Id3 specifically in B cells regulates an atheroprotective subset.
Methods: To determine the impact of loss of Id3 specifically in B cells, we generated B cell specific Id3 knockout mice on the Apoe-/- background (Id3fl/flApoe-/-CD19cre/+). To measure atherosclerosis, 8 week old male Id3fl/flApoe-/-CD19cre/+ mice were fed Western diet for 16 weeks (n=7). These mice developed significantly less atherosclerosis in the aortic sinus compared to litter matched wildtype controls (Id3fl/flApoe-/-CD19+/+, n=10) suggesting loss of Id3 in B cells was atheroprotective. Additionally, immunohistochemistry of atherosclerotic plaques demonstrated decreased intraplaque macrophage accumulation and fewer apoptotic bodies compared to wildtype. Immunophenotyping of Id3fl/flApoe-/-CD19cre/+ mice by flow cytometry revealed a specific increase of B1b B cells in the peritoneal cavity, spleen, and in circulation compared to wildtype (n=12-19). Additionally, 8 week old Id3fl/flApoe-/-CD19cre/+ mice (n=8) were shown by ELISA to have significantly greater circulating IgM and, after 16 weeks of Western diet feeding (n=10), significantly greater circulating natural antibodies compared to wildtype (n= 9 & 11 respectively).
Conclusion: B cell-specific loss of Id3 enhances the B1b B cell pool, natural antibody production, and atheroprotection suggesting B1b B cells are important in defending against atherosclerosis in an antibody dependent manner.
Author Disclosures: S. Morris-Rosenfeld: None. H.M. Perry: None. C.A. McNamara: None.
- © 2014 by American Heart Association, Inc.