急性 SARS-CoV-2 感染期间的浆细胞反应

M. Byazrova, M. Sukhova, A. Mikhailov, A. F. Romanova, G. M. Yusubaliyeva, A. Filatov
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引用次数: 0

摘要

浆细胞是一种寿命较短的 B 细胞,在接种疫苗后不久和急性感染期间出现在血液循环中。浆细胞由静止的 B 淋巴细胞形成,它们分泌抗体的能力与静止的 B 淋巴细胞不同,因此与浆细胞相似。浆细胞是终末分化的细胞,可在 B 细胞反应的不同节点和分支形成。浆细胞反应是疫苗接种成功与否的一个指标,也有助于预测恢复或接种疫苗后的抗体水平。然而,质母细胞的定义和分类面临着巨大的实验和理论困难。这项工作的目的是确定急性 SARS-CoV-2 感染期间浆细胞反应的特征。研究对象包括 COVID-19 重症患者(28 人)。在住院后的第 10-18 天抽血一次。用免疫磁分离法分离 B 细胞。使用流式细胞仪对细胞进行表型分析。用 ELISpot 法测定 IgM 和 IgG 的分泌量。使用细胞分拣机分离 B 细胞亚群。与健康供体相比,COVID-19 患者的总浆细胞水平增加了约四倍。与阴性对照相比,RBD特异性浆细胞的超标更为明显。就其组成而言,浆细胞中有三分之一是 IgM⁺细胞。这种 B 细胞 BCR 受体异型间的分布与 COVID-19 免疫反应的主要性质一致。大约三分之一的浆细胞携带 CD138 抗原。CD138 标记是浆细胞成熟晚期的特征,也存在于浆细胞上。我们根据 CD138 抗原的表达情况对 CD27+CD38⁺ 群体进行了划分。通过 ELISpot 方法,我们发现循环浆细胞中有很大一部分是分泌抗体的细胞。在循环浆细胞中,可以区分早期和晚期浆细胞,它们的特点是没有表面BCR,但携带CD138抗原。确定血浆母细胞与其他 B 细胞群的关系,对于开发 COVID-19 的新疗法和研制有希望的 SARS-CoV-2 感染疫苗至关重要。
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Plasmablast response during acute SARS-CoV-2 infection
Plasmablasts are a population of short-lived B cells that appear in the circulation shortly after vaccination and during acute infection. Plasmablasts are formed from resting B lymphocytes, from which they differ in their ability to secrete antibodies, making them similar to plasma cells. Plasmablasts are terminally differentiated cells that can form at various nodes and branches of the B cell response. The plasmablast response is an indicator of the success of vaccination and also helps in predicting antibody levels after recovery or vaccination. However, the definition and classification of plasmablasts faces great experimental and theoretical difficulties. The aim of the work was to determine the characteristics of the plasmablast response during acute SARS-CoV-2 infection. The study included patients (n = 28) with a severe form of COVID-19. Blood sampling was carried out once on the 10–18th day from the moment of hospitalization. B cells were isolated by immunomagnetic separation. Cells were phenotyped using flow cytometry. Secretion of IgM and IgG was determined by ELISpot method. B cell subsets were isolated using a cell sorter. Patients with COVID-19 had an approximately fourfold increase in total plasmablast levels compared to healthy donors. An even more pronounced excess over the negative control was observed for RBD-specific plasmablasts. In terms of their composition, plasmablasts were one third IgM⁺ cells. This distribution between B-cell BCR receptor isotypes was consistent with the primary nature of the immune response in COVID-19. Approximately a third of plasmablasts carried the CD138 antigen. CD138 marker is characteristic of the late stage of plasmablast maturation and is also found on plasma cells. The CD27+CD38⁺ population was divided according to the expression of the CD138 antigen. Using the ELISpot method, we have shown that a significant portion of circulating plasmablasts are antibody-secreting cells. Among circulating plasmablasts, both early and late plasmablasts can be distinguished, which are characterized by the absence of a surface BCR, but which carry the CD138 antigen. Determining how plasmablasts relate to other B cell populations is of paramount importance for the development of new treatments for COVID-19 and for the creation of promising vaccines against SARS-CoV-2 infection.
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