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Deep sequencing reveals the skewed B-cell receptor repertoire in plaques and the association between pathogens and atherosclerosis
Cellular Immunology ( IF 4.3 ) Pub Date : 2020-12-11 , DOI: 10.1016/j.cellimm.2020.104256
Shucui Zhang 1 , Shigang Zhang 2 , Zongwei Lin 1 , Xinjie Zhang 3 , Xinyao Dou 3 , Xiaoming Zhou 4 , Xiaowei Wang 1 , Zhe Wang 4 , Qunye Zhang 1
Affiliation  

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.



中文翻译:

深度测序揭示了斑块中偏斜的B细胞受体库,以及病原体与动脉粥样硬化之间的关联

B细胞调节的免疫/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细胞功能中起关键作用。然而,动脉粥样硬化患者中BCR组成的组成和分子特征尚未完全阐明。在这里,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的血液循环和斑块中的BCR组成。我们的数据表明,在斑块中,BCR的库显着偏斜,其组合和多样性显着降低,而公共B细胞和优势B细胞克隆的频率显着增加。另外,斑块中的BCRH CDR3具有比正常受试者和动脉粥样硬化患者的外周血中更高的阳性选择压力。甲型流感病毒,暗示病原体与动脉粥样硬化之间存在关联。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细胞克隆的特异性抗体的设计可能产生有用的工具,以揭示动脉粥样硬化的发病机理,评估或减轻动脉粥样硬化的进展。

更新日期:2020-12-22
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