论文标题
B细胞曲目的动力学和在疾病严重程度不同的COVID患者中的交叉反应反应的出现
Dynamics of B-cell repertoires and emergence of cross-reactive responses in COVID-19 patients with different disease severity
论文作者
论文摘要
COVID-19患者显示，这种疾病的严重程度从无症状到需要重症监护剂的疾病严重程度不同。尽管已经确定了许多SARS-COV-2特异性单克隆抗体，但我们仍然缺乏对Covid-19患者中B细胞受体（BCR）曲目的总体景观的了解。在这里，我们使用了在感染过程中在多个时间点收集的大量和等离子体B细胞的高通量测序，以表征B细胞对SARS-COV-2反应的特征，其中19例患者中的SARS-COV-2。使用原则性的统计方法，我们确定了与不同疾病严重程度相关的BCR的差异特征。我们确定了38位患者共享的克隆谱系显着扩展，作为对SARS-COV-2的特定反应的候选者。使用单细胞测序，我们验证了个体之间对SARS-COV-2表位共享的BCR的反应性。此外，我们确定了许多患者在SARS-COV-1和SARS-COV-2上具有交叉反应性的BCR的自然出现。我们的结果为开发有理疗法和针对Covid-19的疫苗提供了重要见解。
COVID-19 patients show varying severity of the disease ranging from asymptomatic to requiring intensive care. Although a number of SARS-CoV-2 specific monoclonal antibodies have been identified, we still lack an understanding of the overall landscape of B-cell receptor (BCR) repertoires in COVID-19 patients. Here, we used high-throughput sequencing of bulk and plasma B-cells collected over multiple time points during infection to characterize signatures of B-cell response to SARS-CoV-2 in 19 patients. Using principled statistical approaches, we determined differential features of BCRs associated with different disease severity. We identified 38 significantly expanded clonal lineages shared among patients as candidates for specific responses to SARS-CoV-2. Using single-cell sequencing, we verified reactivity of BCRs shared among individuals to SARS-CoV-2 epitopes. Moreover, we identified natural emergence of a BCR with cross-reactivity to SARS-CoV-1 and SARS-CoV-2 in a number of patients. Our results provide important insights for development of rational therapies and vaccines against COVID-19.
