SARS-CoV-2 infection causes immunodeficiency in recovered patients by downregulating CD19 expression in B cells via enhancing B-cell metabolism

Abstract The SARS-CoV-2 infection causes severe immune disruption. However, it is unclear if disrupted immune regulation still exists and pertains in recovered COVID-19 patients. In our study, we have characterized the immune phenotype of B cells from 15 recovered COVID-19 patients, and found that h...

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Main Authors: Yukai Jing, Li Luo, Ying Chen, Lisa S. Westerberg, Peng Zhou, Zhiping Xu, Andrés A. Herrada, Chan-Sik Park, Masato Kubo, Heng Mei, Yu Hu, Pamela Pui-Wah Lee, Bing Zheng, Zhiwei Sui, Wei Xiao, Quan Gong, Zhongxin Lu, Chaohong Liu
Format: Article
Language:English
Published: Nature Publishing Group 2021-09-01
Series:Signal Transduction and Targeted Therapy
Online Access:https://doi.org/10.1038/s41392-021-00749-3
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author Yukai Jing
Li Luo
Ying Chen
Lisa S. Westerberg
Peng Zhou
Zhiping Xu
Andrés A. Herrada
Chan-Sik Park
Masato Kubo
Heng Mei
Yu Hu
Pamela Pui-Wah Lee
Bing Zheng
Zhiwei Sui
Wei Xiao
Quan Gong
Zhongxin Lu
Chaohong Liu
author_facet Yukai Jing
Li Luo
Ying Chen
Lisa S. Westerberg
Peng Zhou
Zhiping Xu
Andrés A. Herrada
Chan-Sik Park
Masato Kubo
Heng Mei
Yu Hu
Pamela Pui-Wah Lee
Bing Zheng
Zhiwei Sui
Wei Xiao
Quan Gong
Zhongxin Lu
Chaohong Liu
author_sort Yukai Jing
collection DOAJ
description Abstract The SARS-CoV-2 infection causes severe immune disruption. However, it is unclear if disrupted immune regulation still exists and pertains in recovered COVID-19 patients. In our study, we have characterized the immune phenotype of B cells from 15 recovered COVID-19 patients, and found that healthy controls and recovered patients had similar B-cell populations before and after BCR stimulation, but the frequencies of PBC in patients were significantly increased when compared to healthy controls before stimulation. However, the percentage of unswitched memory B cells was decreased in recovered patients but not changed in healthy controls upon BCR stimulation. Interestingly, we found that CD19 expression was significantly reduced in almost all the B-cell subsets in recovered patients. Moreover, the BCR signaling and early B-cell response were disrupted upon BCR stimulation. Mechanistically, we found that the reduced CD19 expression was caused by the dysregulation of cell metabolism. In conclusion, we found that SARS-CoV-2 infection causes immunodeficiency in recovered patients by downregulating CD19 expression in B cells via enhancing B-cell metabolism, which may provide a new intervention target to cure COVID-19.
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spelling doaj.art-35a91ff1e9094bd4a733b8cae92b770c2022-12-21T21:35:41ZengNature Publishing GroupSignal Transduction and Targeted Therapy2059-36352021-09-016111310.1038/s41392-021-00749-3SARS-CoV-2 infection causes immunodeficiency in recovered patients by downregulating CD19 expression in B cells via enhancing B-cell metabolismYukai Jing0Li Luo1Ying Chen2Lisa S. Westerberg3Peng Zhou4Zhiping Xu5Andrés A. Herrada6Chan-Sik Park7Masato Kubo8Heng Mei9Yu Hu10Pamela Pui-Wah Lee11Bing Zheng12Zhiwei Sui13Wei Xiao14Quan Gong15Zhongxin Lu16Chaohong Liu17Department of Medical Laboratory, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Pathogen Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and TechnologyCenter for Biosafety Mega-Science, Wuhan Institute of Virology, Chinese Academy of SciencesDepartment of Microbiology Tumor and Cell Biology, Karolinska InstituteCenter for Biosafety Mega-Science, Wuhan Institute of Virology, Chinese Academy of SciencesWuhan Metware Biotechnology Co., LtdLymphatic and Inflammation Research Laboratory, Facultad de Ciencias de la Salud, Instituto de Ciencias Biomédicas, Universidad Autónoma de ChileDepartment of Pathology, Asan Medical Center, University of Ulsan College of MedicineLaboratory for Cytokine Regulation, Center for Integrative Medical Science (IMS), RIKEN Yokohama InstituteInstitute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyInstitute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Paediatrics and Adolescent Medicine, LKS Faculty of Medicine, The University of Hong KongDepartment of Immunology, School of Medicine, Yangtze UniversityCenter for Advanced Measurement Science, National Institute of MetrologyDepartment of Respiratory, The First Affiliated Hospital of Yangtze UniversityDepartment of Immunology, School of Medicine, Yangtze UniversityDepartment of Medical Laboratory, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Pathogen Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and TechnologyAbstract The SARS-CoV-2 infection causes severe immune disruption. However, it is unclear if disrupted immune regulation still exists and pertains in recovered COVID-19 patients. In our study, we have characterized the immune phenotype of B cells from 15 recovered COVID-19 patients, and found that healthy controls and recovered patients had similar B-cell populations before and after BCR stimulation, but the frequencies of PBC in patients were significantly increased when compared to healthy controls before stimulation. However, the percentage of unswitched memory B cells was decreased in recovered patients but not changed in healthy controls upon BCR stimulation. Interestingly, we found that CD19 expression was significantly reduced in almost all the B-cell subsets in recovered patients. Moreover, the BCR signaling and early B-cell response were disrupted upon BCR stimulation. Mechanistically, we found that the reduced CD19 expression was caused by the dysregulation of cell metabolism. In conclusion, we found that SARS-CoV-2 infection causes immunodeficiency in recovered patients by downregulating CD19 expression in B cells via enhancing B-cell metabolism, which may provide a new intervention target to cure COVID-19.https://doi.org/10.1038/s41392-021-00749-3
spellingShingle Yukai Jing
Li Luo
Ying Chen
Lisa S. Westerberg
Peng Zhou
Zhiping Xu
Andrés A. Herrada
Chan-Sik Park
Masato Kubo
Heng Mei
Yu Hu
Pamela Pui-Wah Lee
Bing Zheng
Zhiwei Sui
Wei Xiao
Quan Gong
Zhongxin Lu
Chaohong Liu
SARS-CoV-2 infection causes immunodeficiency in recovered patients by downregulating CD19 expression in B cells via enhancing B-cell metabolism
Signal Transduction and Targeted Therapy
title SARS-CoV-2 infection causes immunodeficiency in recovered patients by downregulating CD19 expression in B cells via enhancing B-cell metabolism
title_full SARS-CoV-2 infection causes immunodeficiency in recovered patients by downregulating CD19 expression in B cells via enhancing B-cell metabolism
title_fullStr SARS-CoV-2 infection causes immunodeficiency in recovered patients by downregulating CD19 expression in B cells via enhancing B-cell metabolism
title_full_unstemmed SARS-CoV-2 infection causes immunodeficiency in recovered patients by downregulating CD19 expression in B cells via enhancing B-cell metabolism
title_short SARS-CoV-2 infection causes immunodeficiency in recovered patients by downregulating CD19 expression in B cells via enhancing B-cell metabolism
title_sort sars cov 2 infection causes immunodeficiency in recovered patients by downregulating cd19 expression in b cells via enhancing b cell metabolism
url https://doi.org/10.1038/s41392-021-00749-3
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