Department of Medical Laboratory, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
Department of Emergency, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, People's Republic of China.
Signal Transduct Target Ther. 2021 Sep 22;6(1):345. doi: 10.1038/s41392-021-00749-3.
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.
SARS-CoV-2 感染会导致严重的免疫紊乱。然而,目前尚不清楚这种免疫调节紊乱是否仍然存在,并与已康复的 COVID-19 患者有关。在我们的研究中,我们对 15 名康复的 COVID-19 患者的 B 细胞免疫表型进行了特征分析,发现健康对照组和康复组患者在 BCR 刺激前后的 B 细胞群体相似,但与健康对照组相比,患者在刺激前的 PBC 频率显著增加。然而,在 BCR 刺激后,恢复组患者的未转换记忆 B 细胞的比例下降,但健康对照组没有变化。有趣的是,我们发现几乎所有恢复组患者的 B 细胞亚群中 CD19 的表达都显著降低。此外,BCR 信号和早期 B 细胞反应在 BCR 刺激后受到干扰。在机制上,我们发现 CD19 表达的降低是由于 B 细胞代谢的失调导致的。总之,我们发现 SARS-CoV-2 感染通过增强 B 细胞代谢下调 B 细胞中的 CD19 表达,从而导致康复患者免疫功能缺陷,这可能为治疗 COVID-19 提供新的干预靶点。