Abstract 665: Perivascular Adipose Tissue near Aortic Arch is a Major Site for Atheroprotective IgM Producing B-1 Cells

Abstract

Background: Perivascular adipose tissue (PVAT) regulates artery physiology and pathology, such as promoting atherosclerosis development through local production of inflammatory cytokines. The phenotype of PVAT is region-specific and PVAT composed of brown adipose tissue (near the aortic arch and thoracic aorta) and white adipose tissue (near the abdominal aorta). B-1 cells limit adipose tissue inflammation and atherosclerosis through the production of IgM antibodies. PVAT harbors high numbers of B cells. Id3 is a basic helix-loop-helix protein and important for B cell development. B cell-specific Id3 deficiency (Id3 BKO ) increases B-1b cell numbers and provides atheroprotection. However, the location and regulation of IgM producing B-1 cells in the PVAT are unknown. Methods and Results: Flow cytometry analysis of PVAT of normal chow diet fed young ApoE -/- mice (n=5) demonstrated that the abundant CD19 + B cells (per gram fat) harbored in PVAT around aortic arch (2.7 + 0.69 x10 5 cells) compared to PVAT near the thoracic (0.9 + 0.29 x10 5 cells) and abdominal aorta (1.1 + 0.51 x10 5 cells). Interestingly, a large proportion (40%) of these B cells are belong to the CD19 hi B220 low B-1 subset in PVAT near aortic arch. CXCL13 is a chemokine, which is important for B-1 cell recruitment to omental fat. Real time-PCR data confirmed that high numbers of B-1 cell recruitment to PVAT near aortic arch is due to high expression of CXCL13 in the PVAT near the aortic arch compared to PVAT near thoracic aorta and abdominal aorta. Moreover, Flow cytometry and ELISPOT data in normal chow fed young ApoE -/- mice with Id3 BKO demonstrated that Id3 BKO increased B-1b cells (Id3 BKO : 1.2 + 0.16 x10 3 ; Id3 WT : 0.4 + 0.06 x10 3 ; p-value: <0.01; n=6 mice/group) and IgM secreting cells (Id3 BKO : 2.0 + 0.42 x10 3 ; Id3 WT : 0.78 + 0.23 x10 3 ; p-value: <0.05; n=6 mice/group) respectively in PVAT near aortic arch compared to Id3 WT control mice. Conclusion: Results provide the first evidence that atheroprotective B-1 cell profile in PVAT is region-specific and identify Id3 and CXCL13 as regulators of aortic arch PVAT B-1b cell numbers and IgM production.