Global characterization of B cell receptor repertoire in COVID-19 patients by single-cell V(D)J sequencing
Global characterization of B cell receptor repertoire in COVID-19 patients by single-cell V(D)J sequencing
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DOI：
10.1093/bib/bbab192
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发表时间：
2021-05-20
影响因子：
9.5
通讯作者：
Jiang, Qinghua
中科院分区：
文献类型：
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作者：
Jin, Xiyun;Zhou, Wenyang;Jiang, Qinghua
全球正面临由严重急性呼吸系统综合征冠状病毒2型（SARS-CoV-2）引起的2019年冠状病毒病（COVID-19）大流行。适应性免疫应答对于SARS-CoV-2病毒清除至关重要。尽管已经进行了大量研究来调查COVID-19患者的免疫机制，但我们仍然缺乏对患者BCR库的全面了解。在这项研究中，我们使用单细胞V（D）J测序来表征恢复期COVID-19患者的BCR库。我们观察到，与健康对照组相比，BCR多样性在疾病中显著降低。在COVID-19和健康对照中，BCR倾向于偏向不同的V基因片段。与健康对照组相比，患者克隆BCR重链CDR 3序列更趋一致。此外，我们发现在疾病中增加的IgG和伊加同种型，包括IgG 1，IgG 3和IgA 1。在所有克隆BCR中，IgG同种型具有最频繁的类别转换重组事件和最高的体细胞超突变率，尤其是IgG 3。此外，我们发现来自不同克隆群的IgG 3簇具有相同的IGHV、IGHJ和CDR 3序列（IGHV 4 -4-CARLANTNQFYDSSSYLNAMDVW-IGHJ 6）。总的来说，我们的研究提供了COVID-19患者BCR库的全面表征，这有助于理解SARS-CoV-2感染的免疫应答机制。
The world is facing a pandemic of Corona Virus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Adaptive immune responses are essential for SARS-CoV-2 virus clearance. Although a large body of studies have been conducted to investigate the immune mechanism in COVID-19 patients, we still lack a comprehensive understanding of the BCR repertoire in patients. In this study, we used the single-cell V(D)J sequencing to characterize the BCR repertoire across convalescent COVID-19 patients. We observed that the BCR diversity was significantly reduced in disease compared with healthy controls. And BCRs tend to skew toward different V gene segments in COVID-19 and healthy controls. The CDR3 sequences of heavy chain in clonal BCRs in patients were more convergent than that in healthy controls. In addition, we discovered increased IgG and IgA isotypes in the disease, including IgG1, IgG3 and IgA1. In all clonal BCRs, IgG isotypes had the most frequent class switch recombination events and the highest somatic hypermutation rate, especially IgG3. Moreover, we found that an IgG3 cluster from different clonal groups had the same IGHV, IGHJ and CDR3 sequences (IGHV4-4-CARLANTNQFYDSSSYLNAMDVW-IGHJ6). Overall, our study provides a comprehensive characterization of the BCR repertoire in COVID-19 patients, which contributes to the understanding of the mechanism for the immune response to SARS-CoV-2 infection.