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新型冠状病毒肺炎患者临床表现各异,B 细胞受体出现偏倚性使用。

Novel skewed usage of B-cell receptors in COVID-19 patients with various clinical presentations.

机构信息

Precision medicine center, The First Affiliated Hospital of Xi'an Jiaotong University, 277 Yanta West Road, Xi'an 710061, China; Center for Molecular Diagnosis and Precision Medicine, and The Department of Clinical Laboratory, The First Affiliated Hospital of Nanchang University,17 Yongwai Zhengjie, Nanchang 330006, China.

Precision medicine center, The First Affiliated Hospital of Xi'an Jiaotong University, 277 Yanta West Road, Xi'an 710061, China; The MED-X Institute, The First Affiliated Hospital of Xi'an Jiaotong University, Building 21, Western China Science and Technology Innovation Harbor, Xi'an 710000, China.

出版信息

Immunol Lett. 2022 Sep;249:23-32. doi: 10.1016/j.imlet.2022.08.006. Epub 2022 Aug 31.

DOI:10.1016/j.imlet.2022.08.006
PMID:36055412
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9428335/
Abstract

B cell-mediated immune responses play important roles in controlling SARS-CoV infection. Here, we performed the single-cell B cell receptor sequencing (scBCR-seq) of the PBMC samples from eleven healthy controls, five asymptomatic subjects and 33 symptomatic COVID-19 patients with various clinical presentations, and subsequently analyzed the abundance and diversity of the BCR repertoires in different groups, respectively. We revealed the skewed usage of the IGHV, IGLV and IGKV genes and identified a number of heavy or light chain VDJ gene pairs and combinational preference in each group, such as IGKV3-7 and IGKV2-24 enriched in the asymptomatic subjects, whereas IGHV3-13, IGHV3-23-IGHJ4, IGHV1-18-IGLV3-19, IGHV1-18-IGLV3-21, and IGHV1-18-IGLV3-25 enriched in the recovery patients with severe diseases. We also observed the differential expression of IGHV3-23 in various B cell clusters by analysis of the scRNA-seq data. Additional dock analysis indicated that IGHV3-13 could bind to the spike protein of SARS-CoV-2. These findings may advance our understanding of the humoral immune responses in COVID-19 patients and help develop novel vaccine candidates as well as therapeutical antibodies against SASR-CoV-2 infections.

摘要

B 细胞介导的免疫反应在控制 SARS-CoV 感染中发挥重要作用。在这里,我们对 11 名健康对照者、5 名无症状感染者和 33 名有不同临床表现的 COVID-19 症状患者的 PBMC 样本进行了单细胞 B 细胞受体测序(scBCR-seq),并分别分析了不同组别中 BCR 库的丰度和多样性。我们揭示了 IGHV、IGLV 和 IGKV 基因的偏倚性使用,并在每个组别中鉴定了大量的重链或轻链 VDJ 基因对和组合偏好,例如在无症状感染者中富集的 IGKV3-7 和 IGKV2-24,而在恢复期中重症患者中富集的 IGHV3-13、IGHV3-23-IGHJ4、IGHV1-18-IGLV3-19、IGHV1-18-IGLV3-21 和 IGHV1-18-IGLV3-25。我们还通过 scRNA-seq 数据分析观察到 IGHV3-23 在各种 B 细胞簇中的差异表达。额外的对接分析表明 IGHV3-13 可以与 SARS-CoV-2 的刺突蛋白结合。这些发现可能有助于我们深入了解 COVID-19 患者的体液免疫反应,并有助于开发针对 SARS-CoV-2 感染的新型疫苗候选物和治疗性抗体。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99a1/9428335/10a41dd06715/gr4_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99a1/9428335/89d548fd16de/gr1_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99a1/9428335/8a300bdf7b74/gr2_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99a1/9428335/905fc858b2e6/gr3_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99a1/9428335/10a41dd06715/gr4_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99a1/9428335/89d548fd16de/gr1_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99a1/9428335/8a300bdf7b74/gr2_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99a1/9428335/905fc858b2e6/gr3_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99a1/9428335/10a41dd06715/gr4_lrg.jpg

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