Deep sequencing reveals the skewed B-cell receptor repertoire in plaques and the association between pathogens and atherosclerosis.

Shucui Zhang, Shigang Zhang, Zongwei Lin, Xinjie Zhang, Xinyao Dou, Xiaoming Zhou, Xiaowei Wang, Zhe Wang, Qunye Zhang

Journal: Cellular immunology 2021;360():104256

PMID: 33360167

Full Text on Elsevier Science View on PubMed

Abstract

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.

Address: 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.; Shandong Experimental High School, Jinan, China.; Division of Endocrinology and Metabolism, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.; Division of Endocrinology and Metabolism, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China. Electronic address: [email protected].; 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. Electronic address: [email protected].

DOI: 10.1016/j.cellimm.2020.104256

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MeSH Terms: Amino Acid Sequence, Atherosclerosis, B-Lymphocytes, China, Complementarity Determining Regions, High-Throughput Nucleotide Sequencing, Humans, Receptors, Antigen, B-Cell