Abstract 50: Absence of L-selectin Affects the Distribution of B Cell Subsets and Local Immune Response in Apoe-/- Aortas
To date, a significant body of evidence implicates the immune system in atherosclerosis. Multiple cell subsets provide a fine tuning of pro-inflammatory and suppressive arms of the immunological response. Studies report that follicular B cells are pro-atherogenic whereas B1a cells play a protective role via T15/E06 antibody production; yet the other B cell subsets have to be explored in atherosclerosis. Thus far, little information is available on the mechanisms behind the regulation of cell subset specific homing during atherogenesis. L-selectin is a homing receptor modulating leukocyte tethering and rolling. To investigate the role of L-selectin in atherosclerosis, we generated 50 week old L-selectin deficient Apoe-/- (Sell-/-Apoe-/-) mice fed a chow diet. A L-selectin deficiency resulted in accelerated atherosclerosis that was accompanied by a 1.3-fold increase in the number of leukocytes within aortas of Sell-/-Apoe-/- mice. In contrast to the elevated total leukocyte cellularity in aortas, Sell-/-Apoe-/- aortas had a 2-fold reduction in B cell content. Importantly, an L-selectin deficiency significantly reduced the percentage and number of B1a and regulatory B (Breg) cells within Sell-/-Apoe-/- compared to Apoe-/- aortas and spleens. Despite reduced numbers of B1a cells we detected a 3.2-fold increase in the splenic mRNA expression of T15/E06 suggesting that B1a cells are hyperactive, but are still unable to reduce atherogenesis in Sell-/-Apoe-/- mice. To further examine the effects of L-selectin deficiency on aortic wall inflammation, we analyzed lymphocyte activation and found elevated mRNA expression of B and T cell activation markers in Sell-/-Apoe-/- aortas. In line with the increased leukocyte cellularity of the aorta, there was a 1.5-fold increase in aortic CD68hi macrophages. These data provide evidence for a functional role of L-selectin in atherosclerosis via the regulation of the content of aortic B1a and Breg cells and the modulation of the local immune response within the aorta. However, it also suggests the functions of B1a and Breg cells can be suppressed by additional factors contributing to accelerated atherosclerosis.
- © 2013 by American Heart Association, Inc.