Carter Immunology Center, University of Virginia, Charlottesville, VA, USA.
Cardiovascular Research Center, University of Virginia, Charlottesville, VA, USA.
Nat Cardiovasc Res. 2023 Nov;2(11):1003-1014. doi: 10.1038/s44161-023-00356-1. Epub 2023 Oct 30.
IgMs that inactivate oxidation-specific epitopes (IgM), which are secondary products of lipid peroxidization, protect against inflammatory diseases, including diet-induced atherosclerosis. However, the human B cell subtype that produces IgM remains unknown. In this study, we used single-cell mass cytometry and adoptive transfer of B cell subtypes to NOD.Cg-Prkdc Il2rg/SzJ (NSG) mice to identify B cells as the major producers of IgM 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 B cells (MZB) in patients inversely correlates with coronary artery disease severity.
IgM 能使氧化特异性抗原表位（IgM）失活，这些抗原表位是脂质过氧化的次级产物，能预防包括饮食诱导的动脉粥样硬化在内的炎症性疾病。然而，产生 IgM 的人类 B 细胞亚型仍不清楚。在这项研究中，我们使用单细胞质谱流式细胞术和 B 细胞亚群的过继转移到 NOD.Cg-Prkdc Il2rg/SzJ（NSG）小鼠中，以鉴定出人类 IgM 的主要产生细胞为 B 细胞。值得注意的是，这些细胞具有人类循环边缘区 B（MZB）细胞的特征，已知 MZB 细胞在小鼠中是一种具有抗动脉粥样硬化作用的 IgM 产生细胞。用 CD24 抗体治疗以减少高脂血症人源化小鼠模型中的 MZB 细胞和 IgM 提供了证据，表明 MZB 细胞可预防血管炎症。与这些发现一致的是，患者 B 细胞（MZB）的频率与冠状动脉疾病的严重程度呈负相关。
