From the Robert M. Berne Cardiovascular Research Center (A.U., C.A.M.), University of Virginia School of Medicine, Charlottesville.
Division of Pulmonary and Critical Care Medicine, Department of Medicine (J.M.S.), University of Virginia School of Medicine, Charlottesville.
Arterioscler Thromb Vasc Biol. 2020 Feb;40(2):309-322. doi: 10.1161/ATVBAHA.119.313064. Epub 2019 Dec 19.
Atherosclerosis-the major underlying pathology of cardiovascular disease-is characterized by accumulation and subsequent oxidative modification of lipoproteins within the artery wall, leading to inflammatory cell infiltration and lesion formation that can over time result in arterial stenosis, ischemia, and downstream adverse events. The contribution of innate and adaptive immunity to atherosclerosis development is well established, and B cells have emerged as important modulators of both pro- and anti-inflammatory effects in atherosclerosis. Murine B cells can broadly be divided into 2 subsets: (1) B-2 cells, which are bone marrow derived and include conventional follicular and marginal zone B cells, and (2) B-1 cells, which are largely fetal liver derived and persist in adults through self-renewal. B-cell subsets are developmentally, functionally, and phenotypically distinct with unique subset-specific contributions to atherosclerosis development. Mechanisms whereby B cells regulate vascular inflammation and atherosclerosis will be discussed with a particular emphasis on B-1 cells. B-1 cells have a protective role in atherosclerosis that is mediated in large part by IgM antibody production. Accumulating evidence over the last several years has pointed to a previously underappreciated heterogeneity in B-1 cell populations, which may have important implications for understanding atherosclerosis development and potential targeted therapeutic approaches. This heterogeneity within atheroprotective innate B-cell subsets will be highlighted.
动脉粥样硬化是心血管疾病的主要潜在病理学特征，其特征是脂蛋白在血管壁内的积累和随后的氧化修饰，导致炎症细胞浸润和病变形成，随着时间的推移可导致动脉狭窄、缺血和下游不良事件。先天免疫和适应性免疫对动脉粥样硬化发展的贡献已得到充分证实，B 细胞已成为动脉粥样硬化中促炎和抗炎作用的重要调节剂。小鼠 B 细胞可大致分为 2 个亚群：(1)B-2 细胞，其由骨髓产生，包括常规滤泡和边缘区 B 细胞，和(2)B-1 细胞，其主要由胎肝产生，并通过自我更新在成人中持续存在。B 细胞亚群在发育、功能和表型上具有独特性，对动脉粥样硬化的发展有独特的亚群特异性贡献。本文将讨论 B 细胞调节血管炎症和动脉粥样硬化的机制，特别强调 B-1 细胞。B-1 细胞在动脉粥样硬化中具有保护作用，主要是通过 IgM 抗体的产生介导的。过去几年积累的证据表明，B-1 细胞群体存在以前未被充分认识的异质性，这可能对理解动脉粥样硬化的发展和潜在的靶向治疗方法有重要意义。本文将重点介绍保护性先天 B 细胞亚群内的这种异质性。
