CXCR5 Surface Marker Expression on Human Circulating Marginal Zone B cells (MZB) is Associated with Atherosclerotic Disease 2256242

Abstract Introduction Cardiovascular disease is the world’s leading killer, emphasizing the need for more effective prevention and treatment strategies. B cells are emerging as key players that modulate atherosclerosis, with recent work from our lab indicating that human circulating MZB produce atheroprotective IgM to oxidation specific epitopes (IgMOSE). However, what markers these cells express and their association with atherosclerosis is largely unknown. Methods To address this, we measured IgM by ELISA and ran a multispectral flow cytometry panel using 47 markers on 212 peripheral blood mononuclear cell samples from patients who had also undergone intravascular ultrasound with atherosclerotic plaque characterization. The mean fluorescence intensity of 15 markers was analyzed on circulating MZB (CD27+IgM+CD21+CD1c+) and correlated with IgM and plaque characteristics. Results CXCR5 on MZB was inversely associated with IgM and positively correlated with atheroma burden (%) which retained significance following adjustment for age, sex, and total cholesterol using multiple linear regression. CCR6, CD161, and ICOS were also found to have significant associations with atheroma burden (%), calcification (%) and necrotic content (%) (respectively) using the same multiple linear regression analysis. Conclusion Specific surface markers on circulating MZB associate with atherosclerosis and plasma IgM levels. Further research is needed to determine their functional significance and utility as clinical biomarkers. Funding Source R01 AI172112, P01 HL136275, R01 HL148109 Topic Categories Cytokines and Chemokines and their Receptors (CCR)