Atheroprotective potential of CXCR4 on B1 cells (CAM4P.145)

Abstract

Abstract Atherosclerosis is a chronic inflammatory condition in which lipid deposition in arteries leads to the recruitment, activation, and accumulation of immune cells in the artery wall. Immune cells can have protective or detrimental effects on disease development. Existing evidence demonstrates that B1 cells hinder atherosclerotic lesion formation by secreting natural IgM antibodies that recognize modified self-epitopes present in diseased arteries. However, the mechanisms underlying B1 cell migration to arteries require further study. Our lab utilizes flow cytometry of circulating human immune cells in patients undergoing intravascular ultrasound of coronary arteries, in order to identify key surface markers that are associated with plaque burden. Expression of the chemokine receptor CXCR4 on human CD20+ CD3- CD27+ CD43+ B1 cells associated with reduced plaque burden in coronary arteries. No correlation was found between plaque volume and CXCR4 expression on naïve or memory B cell subsets. Prior evidence demonstrates that the helix-loop-helix transcription factor Id3 regulates B cell homing to the aorta and B cell-mediated atheroprotection. Loss of Id3 in the Apoe-/- mouse model of atherosclerosis led to systemic increase in surface expression of CXCR4 on B1 cells. Loss of Id3 additionally led to attenuated lesion formation, as measured by immunohistochemical lesion analysis of the aorta. These data suggest a potential atheroprotective function of CXCR4 on B1 cells.