학술논문

Human circulating CD24hi marginal zone B cells produce IgM targeting atherogenic antigens and confer protection from vascular disease
Document Type
Original Paper
Source
Nature Cardiovascular Research. 2(11):1003-1014
Subject
Language
English
ISSN
2731-0590
Abstract
IgMs that inactivate oxidation-specific epitopes (IgMOSE), which are secondary products of lipid peroxidization, protect against inflammatory diseases, including diet-induced atherosclerosis. However, the human B cell subtype that produces IgMOSE remains unknown. In this study, we used single-cell mass cytometry and adoptive transfer of B cell subtypes to NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ (NSG) mice to identify B27+IgM+CD24hi cells as the major producers of IgMOSE in humans. Notably, these cells have characteristics of human circulatory marginal zone B (MZB) cells, which are known to be atheoroprotective IgM producers in mice. CD24 antibody treatment to reduce MZB cells and IgM in a hyperlipidemic humanized mouse model provides the evidence that MZB cells protect against vascular inflammation. Consistent with these findings, the frequency of B27+IgM+CD24hi cells (MZB) in patients inversely correlates with coronary artery disease severity.
By single-cell mass cytometry and adoptive transfer of B cell subtypes in mice, Pattarabanjird et al. show that human CD24hi circulating marginal zone B cells produce IgM to atherosclerosis antigens and confer atheroprotection. Blocking CD24 increased vascular inflammation in hyperlipidemic humanized mice.