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S Protein-Reactive IgG and Memory B Cell Production after Human SARS-CoV-2 Infection Includes Broad Reactivity to the S2 Subunit
mBio ( IF 6.4 ) Pub Date : 2020-09-25 , DOI: 10.1128/mbio.01991-20 Phuong Nguyen-Contant 1 , A. Karim Embong 1 , Preshetha Kanagaiah 1 , Francisco A. Chaves 1 , Hongmei Yang 2 , Angela R. Branche 3 , David J. Topham 1 , Mark Y. Sangster 1
mBio ( IF 6.4 ) Pub Date : 2020-09-25 , DOI: 10.1128/mbio.01991-20 Phuong Nguyen-Contant 1 , A. Karim Embong 1 , Preshetha Kanagaiah 1 , Francisco A. Chaves 1 , Hongmei Yang 2 , Angela R. Branche 3 , David J. Topham 1 , Mark Y. Sangster 1
Affiliation
The high susceptibility of humans to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the cause of coronavirus disease 2019 (COVID-19), reflects the novelty of the virus and limited preexisting B cell immunity. IgG against the SARS-CoV-2 spike (S) protein, which carries the novel receptor binding domain (RBD), is absent or at low levels in unexposed individuals. To better understand the B cell response to SARS-CoV-2 infection, we asked whether virus-reactive memory B cells (MBCs) were present in unexposed subjects and whether MBC generation accompanied virus-specific IgG production in infected subjects. We analyzed sera and peripheral blood mononuclear cells (PBMCs) from non-SARS-CoV-2-exposed healthy donors and COVID-19 convalescent subjects. Serum IgG levels specific for SARS-CoV-2 proteins (S, including the RBD and S2 subunit, and nucleocapsid [N]) and non-SARS-CoV-2 proteins were related to measurements of circulating IgG MBC levels. Anti-RBD IgG was absent in unexposed subjects. Most unexposed subjects had anti-S2 IgG, and a minority had anti-N IgG, but IgG MBCs with these specificities were not detected, perhaps reflecting low frequencies. Convalescent subjects had high levels of IgG against the RBD, S2, and N, together with large populations of RBD- and S2-reactive IgG MBCs. Notably, IgG titers against the S protein of the human coronavirus OC43 were higher in convalescent subjects than in unexposed subjects and correlated strongly with anti-S2 titers. Our findings indicate cross-reactive B cell responses against the S2 subunit that might enhance broad coronavirus protection. Importantly, our demonstration of MBC induction by SARS-CoV-2 infection suggests that a durable form of B cell immunity is maintained even if circulating antibody levels wane.
中文翻译:
人SARS-CoV-2感染后S蛋白反应性IgG和记忆B细胞的产生包括对S2亚基的广泛反应
人类对严重急性呼吸系统综合症冠状病毒2(SARS-CoV-2)感染的高度敏感性是2019年冠状病毒病的病因(COVID-19),反映了该病毒的新颖性和有限的既有B细胞免疫力。在未暴露的个体中,不存在抗SARS-CoV-2穗蛋白(S)的IgG,该蛋白带有新的受体结合域(RBD)。为了更好地理解B细胞对SARS-CoV-2感染的反应,我们询问未暴露的受试者中是否存在病毒反应性记忆B细胞(MBC),以及在感染的受试者中MBC的产生是否伴随病毒特异性IgG的产生。我们分析了来自未暴露SARS-CoV-2的健康供体和COVID-19康复期受试者的血清和外周血单核细胞(PBMC)。对SARS-CoV-2蛋白具有特异性的血清IgG水平(S,包括RBD和S2亚基,以及核衣壳[N]和非SARS-CoV-2蛋白与循环IgG MBC水平的测量有关。未暴露的受试者中不存在抗-RBD IgG。大多数未暴露的受试者具有抗S2 IgG,而少数受试者具有抗N IgG,但是未检测到具有这些特异性的IgG MBC,可能反映了低频。康复中的受试者对RBD,S2和N的IgG含量较高,同时还有大量的RBD和S2反应性IgG MBC。值得注意的是,康复期受试者抗人冠状病毒OC43 S蛋白的IgG滴度高于未接触受试者,并且与抗S2滴度密切相关。我们的发现表明,针对S2亚基的交叉反应性B细胞反应可能增强了冠状病毒的广泛保护。重要的,
更新日期:2020-10-28
中文翻译:
人SARS-CoV-2感染后S蛋白反应性IgG和记忆B细胞的产生包括对S2亚基的广泛反应
人类对严重急性呼吸系统综合症冠状病毒2(SARS-CoV-2)感染的高度敏感性是2019年冠状病毒病的病因(COVID-19),反映了该病毒的新颖性和有限的既有B细胞免疫力。在未暴露的个体中,不存在抗SARS-CoV-2穗蛋白(S)的IgG,该蛋白带有新的受体结合域(RBD)。为了更好地理解B细胞对SARS-CoV-2感染的反应,我们询问未暴露的受试者中是否存在病毒反应性记忆B细胞(MBC),以及在感染的受试者中MBC的产生是否伴随病毒特异性IgG的产生。我们分析了来自未暴露SARS-CoV-2的健康供体和COVID-19康复期受试者的血清和外周血单核细胞(PBMC)。对SARS-CoV-2蛋白具有特异性的血清IgG水平(S,包括RBD和S2亚基,以及核衣壳[N]和非SARS-CoV-2蛋白与循环IgG MBC水平的测量有关。未暴露的受试者中不存在抗-RBD IgG。大多数未暴露的受试者具有抗S2 IgG,而少数受试者具有抗N IgG,但是未检测到具有这些特异性的IgG MBC,可能反映了低频。康复中的受试者对RBD,S2和N的IgG含量较高,同时还有大量的RBD和S2反应性IgG MBC。值得注意的是,康复期受试者抗人冠状病毒OC43 S蛋白的IgG滴度高于未接触受试者,并且与抗S2滴度密切相关。我们的发现表明,针对S2亚基的交叉反应性B细胞反应可能增强了冠状病毒的广泛保护。重要的,