The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.
Neurosurgical Department, Liaocheng People's Hospital, Liaocheng, China.
Cell Immunol. 2021 Feb;360:104256. doi: 10.1016/j.cellimm.2020.104256. Epub 2020 Dec 11.
The immune/inflammatory responses regulated by B cells are the critical determinants of atherosclerosis. B-cell receptor (BCR) plays pivotal roles in regulating B cell function. However, the composition and molecular characteristics of the BCR repertoire in atherosclerotic patients have not been fully elucidated. Herein we analyzed BCR repertoire in circulation and plaques of atherosclerotic patients by sequencing the BCR heavy chain complement determining region 3 (BCRH CDR3). Our data showed that in plaques, BCR repertoire was dramatically skewed and their combinations and diversity were significantly decreased, while the frequency of public and dominant B-cell clones was markedly increased. Additionally, BCRH CDR3 in plaques had higher positive selection pressure than that in the peripheral blood of normal subjects and atherosclerotic patients. Moreover, the BCRH CDR3 of some B cell clones specifically expanded in plaques were similar to that of antibodies which recognized certain pathogens including Influenza A virus, implying the possibility of the association between pathogens and atherosclerosis. The present study contributed to understand the roles of B cells in atherosclerosis. The design of specific antibodies based on the B cell clones specifically expanded in plaques might yield useful tools to reveal the pathogenesis of atherosclerosis, assess or alleviate the progression of atherosclerosis.
B 细胞调控的免疫/炎症反应是动脉粥样硬化的关键决定因素。B 细胞受体（BCR）在调节 B 细胞功能方面发挥着关键作用。然而，动脉粥样硬化患者 BCR 库的组成和分子特征尚未完全阐明。在此，我们通过对 BCR 重链互补决定区 3（BCRH CDR3）进行测序，分析了动脉粥样硬化患者循环和斑块中的 BCR 库。我们的数据表明，在斑块中，BCR 库明显偏向，其组合和多样性显著降低，而公共和优势 B 细胞克隆的频率明显增加。此外，与正常人和动脉粥样硬化患者外周血相比，斑块中的 BCRH CDR3 具有更高的正选择压力。此外，某些在斑块中特异性扩增的 B 细胞克隆的 BCRH CDR3 与识别某些病原体（包括甲型流感病毒）的抗体相似，这表明病原体与动脉粥样硬化之间存在关联的可能性。本研究有助于了解 B 细胞在动脉粥样硬化中的作用。基于在斑块中特异性扩增的 B 细胞克隆设计的特异性抗体可能为揭示动脉粥样硬化的发病机制、评估或减轻动脉粥样硬化的进展提供有用的工具。
