Absence of L-selectin accelerates atherosclerosis via the modulation of B cell subsets and local immune response within the aortas of L-selectin-deficient Apoe-/- mice. (CAM1P.236)

To date, a significant body of evidence implicates the immune system in atherosclerosis. Studies report that follicular B cells are pro-atherogenic whereas B1a cells play a protective role; yet the role of other B cell subsets is unclear. The mechanisms behind the regulation of cell subset specific homing into aortas are not well understood. To determine the role of L-selectin in atherosclerosis, we bred L-selectin deficient (Sell-/-) and Apoe-/- mice and generated Sell-/-Apoe-/- mice. 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. However, Sell-/-Apoe-/- aortas displayed a 2-fold reduction in aortic B cells. Importantly, 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. We found more B1a expressing L-selectin compared with splenic FO B cells, suggesting a potentially high dependence of B1a cells from L-selectin. With the reduction of aortic B1a and Breg, there were reduced IL-10 levels in Sell-/-Apoe-/- aortas. In line with the increased aortic leukocyte cellularity, 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.