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

SARS-CoV-2 infection causes immunodeficiency in recovered patients by downregulating CD19 expression in B cells via enhancing B-cell metabolism.
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DOI:
10.1038/s41392-021-00749-3
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发表时间:
2021-09-22
影响因子:
39.3
通讯作者:
Liu C
Liu C
中科院分区:
医学1区
文献类型:
--
作者:
Jing Y;Luo L;Chen Y;Westerberg LS;Zhou P;Xu Z;Herrada AA;Park CS;Kubo M;Mei H;Hu Y;Lee PP;Zheng B;Sui Z;Xiao W;Gong Q;Lu Z;Liu C

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新冠病毒(SARS-CoV-2)感染会导致严重的免疫紊乱。然而,目前尚不清楚康复的新冠肺炎患者体内是否仍存在免疫调节紊乱的情况。在我们的研究中,我们对15名康复的新冠肺炎患者的B细胞免疫表型进行了分析,发现健康对照组和康复患者在B细胞受体(BCR)刺激前后的B细胞群体相似,但在刺激前,患者中浆母细胞(PBC)的频率与健康对照组相比显著增加。然而,在BCR刺激后,康复患者中未转换记忆B细胞的百分比降低,而健康对照组则无变化。有趣的是,我们发现康复患者几乎所有B细胞亚群中的CD19表达均显著降低。此外,BCR刺激时,BCR信号传导和早期B细胞反应受到干扰。从机制上看,我们发现CD19表达降低是由细胞代谢失调所致。总之,我们发现新冠病毒感染通过增强B细胞代谢而下调B细胞中的CD19表达,从而导致康复患者出现免疫缺陷,这可能为治愈新冠肺炎提供一个新的干预靶点。
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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