Dynamics of B cell repertoires and emergence of cross-reactive responses in patients with different severities of COVID-19.
Dynamics of B cell repertoires and emergence of cross-reactive responses in patients with different severities of COVID-19.
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DOI：
10.1016/j.celrep.2021.109173
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发表时间：
2021-05-25
期刊：
影响因子：
8.8
通讯作者：
Mok CKP
中科院分区：
文献类型：
--
作者：
Montague Z;Lv H;Otwinowski J;DeWitt WS;Isacchini G;Yip GK;Ng WW;Tsang OT;Yuan M;Liu H;Wilson IA;Peiris JSM;Wu NC;Nourmohammad A;Mok CKP
患有2019冠状病毒病（COVID-19）的个体显示出不同的疾病严重程度，从无症状到需要重症监护。尽管已经鉴定出了针对严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）的特异性单克隆抗体，但我们仍然缺乏对COVID-19患者B细胞受体（BCR）库整体情况的了解。我们使用高通量测序的散装和血浆B细胞收集在感染过程中的多个时间点的特征的B细胞对SARS-CoV-2在19个人的签名。使用原则性统计方法，我们将BCR的差异特征与不同的疾病严重程度相关联。我们确定了38个显着扩大的克隆谱系之间共享的个人作为候选人的反应特异性SARS-CoV-2。使用单细胞测序，我们验证了个体之间共享的BCR对SARS-CoV-2表位的反应性。此外，我们确定了自然出现的BCR与SARS-CoV-1和SARS-CoV-2的交叉反应，在一些人。我们的研究结果为开发针对COVID-19的合理疗法和疫苗提供了重要见解。具有SARS-CoV-2表位分选的B细胞受体的B细胞谱系分析B细胞受体的差异序列特征与疾病严重程度相关响应SARS-CoV-2的B细胞克隆谱系扩增共享B细胞受体出现与SARS-CoV-1和SARS-CoV-2的交叉反应性目前尚不清楚SARS-CoV-1和SARS-CoV-2的体液免疫应答动力学如何与SARS-CoV-1和SARS-CoV-2相关。2在不同疾病严重程度的个体之间存在差异。Montague等人开发基于时间进程、高通量B细胞库序列的原则性统计方法，以鉴定共享的、扩增的、罕见的克隆B细胞谱系作为SARS-CoV-2特异性应答的候选者。
Individuals with the 2019 coronavirus disease (COVID-19) show varying severity of the disease, ranging from asymptomatic to requiring intensive care. Although monoclonal antibodies specific to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been identified, we still lack an understanding of the overall landscape of B cell receptor (BCR) repertoires in individuals with COVID-19. We use high-throughput sequencing of bulk and plasma B cells collected at multiple time points during infection to characterize signatures of the B cell response to SARS-CoV-2 in 19 individuals. Using principled statistical approaches, we associate differential features of BCRs with different disease severity. We identify 38 significantly expanded clonal lineages shared among individuals as candidates for responses specific to SARS-CoV-2. Using single-cell sequencing, we verify the reactivity of BCRs shared among individuals to SARS-CoV-2 epitopes. Moreover, we identify the natural emergence of a BCR with cross-reactivity to SARS-CoV-1 and SARS-CoV-2 in some individuals. Our results provide insights important for development of rational therapies and vaccines against COVID-19. Analysis of B cell repertoires with SARS-CoV-2 epitope-sorted B cell receptors Differential sequence features of B cell receptors are associated with disease severity Expansion of B cell clonal lineages in response to SARS-CoV-2 Shared B cell receptors emerge with cross-reactivity to SARS-CoV-1 and SARS-CoV-2 It is unclear how the dynamics of the humoral immune response to SARS-CoV-2 vary across individuals with different disease severity. Montague et al. develop a principled statistical approach based on time-course, high-throughput B cell repertoire sequences to identify shared, expanding, rare clonal B cell lineages as candidates for responses specific to SARS-CoV-2.
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影响因子：
2.7
作者：
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通讯作者：
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DOI：
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发表时间：
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影响因子：
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