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对 COVID-19 患者的 B 细胞受体库进行深度测序揭示了强烈的趋同免疫特征。

Deep Sequencing of B Cell Receptor Repertoires From COVID-19 Patients Reveals Strong Convergent Immune Signatures.

机构信息

Alchemab Therapeutics Ltd, London, United Kingdom.

Wellcome Centre for Human Genetics, Oxford, United Kingdom.

出版信息

Front Immunol. 2020 Dec 15;11:605170. doi: 10.3389/fimmu.2020.605170. eCollection 2020.

Abstract

Deep sequencing of B cell receptor (BCR) heavy chains from a cohort of 31 COVID-19 patients from the UK reveals a stereotypical naive immune response to SARS-CoV-2 which is consistent across patients. Clonal expansion of the B cell population is also observed and may be the result of memory bystander effects. There was a strong convergent sequence signature across patients, and we identified 1,254 clonotypes convergent between at least four of the COVID-19 patients, but not present in healthy controls or individuals following seasonal influenza vaccination. A subset of the convergent clonotypes were homologous to known SARS and SARS-CoV-2 spike protein neutralizing antibodies. Convergence was also demonstrated across wide geographies by comparison of data sets between patients from UK, USA, and China, further validating the disease association and consistency of the stereotypical immune response even at the sequence level. These convergent clonotypes provide a resource to identify potential therapeutic and prophylactic antibodies and demonstrate the potential of BCR profiling as a tool to help understand patient responses.

摘要

对来自英国的 31 名 COVID-19 患者的 B 细胞受体 (BCR) 重链进行深度测序,揭示了对 SARS-CoV-2 的典型幼稚免疫反应,在患者中具有一致性。还观察到 B 细胞群体的克隆扩增,这可能是记忆旁观者效应的结果。患者之间存在强烈的趋同序列特征,我们鉴定了至少 4 名 COVID-19 患者之间具有 1,254 个克隆型趋同,但不存在于健康对照或季节性流感疫苗接种者中。趋同克隆型的一部分与已知的 SARS 和 SARS-CoV-2 刺突蛋白中和抗体具有同源性。通过比较来自英国、美国和中国的患者之间的数据集,在广泛的地理区域也证明了趋同,进一步验证了疾病相关性和即使在序列水平上也具有一致性的典型免疫反应。这些趋同克隆型为鉴定潜在的治疗和预防抗体提供了资源,并证明了 BCR 分析作为帮助理解患者反应的工具的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1faf/7769841/9c63b2622cb4/fimmu-11-605170-g001.jpg

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