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

被引：35

作者：

Jing, Yukai ^{[1
,2
,3
]}

Luo, Li ^{[4
]}

Chen, Ying ^{[5
]}

Westerberg, Lisa S. ^{[6
]}

Zhou, Peng ^{[5
]}

Xu, Zhiping ^{[7
]}

Herrada, Andres A. ^{[8
]}

Park, Chan-Sik ^{[9
]}

Kubo, Masato ^{[10
]}

Mei, Heng ^{[11
]}

Hu, Yu ^{[11
]}

Lee, Pamela Pui-Wah ^{[12
]}

Zheng, Bing ^{[13
,14
]}

Sui, Zhiwei ^{[15
]}

Xiao, Wei ^{[16
]}

Gong, Quan ^{[13
,14
]}

Lu, Zhongxin ^{[1
]}

Liu, Chaohong ^{[4
]}

机构：

[1] Huazhong Univ Sci & Technol, Cent Hosp Wuhan, Tongji Med Coll, Dept Med Lab, Wuhan, Peoples R China

[2] Shanxi Med Univ, Shanxi Bethune Hosp, Tongji Shanxi Hosp, Shanxi Acad Med Sci,Dept Emergency,Hosp 3, Taiyuan, Peoples R China

[3] Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Wuhan, Peoples R China

[4] Huazhong Univ Sci & Technol, Tongji Med Coll, Sch Basic Med, Dept Pathogen Biol, Wuhan, Peoples R China

[5] Chinese Acad Sci, Ctr Biosafety Megasci, Wuhan Inst Virol, Wuhan, Peoples R China

[6] Karolinska Inst, Dept Microbiol Tumor & Cell Biol, Stockholm, Sweden

[7] Wuhan Metware Biotechnol Co Ltd, Wuhan, Peoples R China

[8] Univ Autonoma Chile, Inst Ciencias Biomed, Lymphat & Inflammat Res Lab, Fac Ciencias Salud, Talca, Chile

[9] Univ Ulsan, Asan Med Ctr, Dept Pathol, Coll Med, Seoul, South Korea

[10] RIKEN, Ctr Integrat Med Sci IMS, Lab Cytokine Regulat, Yokohama Inst, Yokohama, Kanagawa, Japan

[11] Huazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Inst Hematol, Wuhan, Peoples R China

[12] Univ Hong Kong, LKS Fac Med, Dept Paediat & Adolescent Med, Hong Kong, Peoples R China

[13] Yangtze Univ, Sch Med, Dept Immunol, Jingzhou, Hubei, Peoples R China

[14] Yangtze Univ, Clin Mol Immunol Ctr, Sch Med, Jingzhou, Hubei, Peoples R China

[15] Natl Inst Metrol, Ctr Adv Measurement Sci, Beijing, Peoples R China

[16] Yangtze Univ, Dept Resp, Affiliated Hosp 1, Jingzhou, Hubei, Peoples R China

来源：

SIGNAL TRANSDUCTION AND TARGETED THERAPY | 2021年 / 6卷 / 01期

基金：

国家重点研发计划; 中国国家自然科学基金;

关键词：

HYPOXIA; LACTATE;

D O I：

10.1038/s41392-021-00749-3

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页数：13

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