Division of Cardiovascular Medicine, Department of Medicine, University of Cambridge, Cambridge, UK.
Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria.
Nat Rev Cardiol. 2019 Mar;16(3):180-196. doi: 10.1038/s41569-018-0106-9.
The cardiovascular system is subject to hyperlipidaemic, inflammatory, and pro-oxidant stressors. Over time, these factors drive prevalent chronic diseases, of which atherosclerosis is most prominent and accounts for the majority of deaths globally. Antibody-producing B cells perform a unique role in responses to stress, injury, and infection. The power, inducibility, and adaptability of the antibody repertoire require an equally complex range of control measures. Defects and chronic perturbations in these checkpoints lead to inappropriate antibody responses, which might have important roles in shaping the development and outcome of atherosclerotic disease. A unique aspect related to atherosclerosis is the prominent role of natural antibodies, specifically those binding to the oxidized epitopes that are abundant on modified lipoproteins and cellular debris. B cells control cellular immune responses through cell-cell contact, antigen presentation, and cytokine production, and thereby participate in systemic and local immune responses in atherosclerotic arteries. To date, both proatherogenic and antiatherogenic properties have been assigned to B cells, depending on subsets and how they are functionally targeted. For these reasons, a deeper understanding of how B cells influence atherosclerotic plaque development is being pursued with the hope of providing novel B cell-targeted interventions to prevent inflammation-driven cardiovascular events.
心血管系统易受到高脂血症、炎症和促氧化应激因素的影响。随着时间的推移,这些因素会引发常见的慢性疾病,其中动脉粥样硬化最为突出,也是导致全球大多数人死亡的主要原因。产生抗体的 B 细胞在应对应激、损伤和感染时发挥着独特的作用。抗体库的强大功能、诱导能力和适应性需要同样复杂的控制措施。这些检查点的缺陷和慢性紊乱会导致不适当的抗体反应,这些反应可能在塑造动脉粥样硬化疾病的发展和结局方面发挥着重要作用。与动脉粥样硬化相关的一个独特方面是天然抗体的突出作用,特别是那些与修饰脂蛋白和细胞碎片上丰富的氧化表位结合的抗体。B 细胞通过细胞间接触、抗原呈递和细胞因子产生来控制细胞免疫反应,从而参与动脉粥样硬化血管的全身和局部免疫反应。迄今为止,根据 B 细胞的亚群和功能靶向方式,B 细胞既有促动脉粥样硬化作用,也有抗动脉粥样硬化作用。基于这些原因,人们正在深入研究 B 细胞如何影响动脉粥样硬化斑块的发展,以期提供新的针对 B 细胞的干预措施来预防炎症驱动的心血管事件。