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Sci Rep . Dominant and cross-reactive S1-specific memory B cell response induced by primary SARS-CoV-2 infection

tetano

Editor, Senior Moderator
Sci Rep


. 2025 Jul 1;15(1):20591.
doi: 10.1038/s41598-025-06847-4. Dominant and cross-reactive S1-specific memory B cell response induced by primary SARS-CoV-2 infection

Xiaomin Xing[SUP] #[/SUP][SUP] 1 2 3 [/SUP], Zhaoyong Zhang[SUP] #[/SUP][SUP] 4 [/SUP], Yingfen Wen[SUP] 1 3 [/SUP], Wenjing Guo[SUP] 1 3 [/SUP], Xulei Zhang[SUP] 1 3 [/SUP], Yuyi Min[SUP] 1 [/SUP], Kexin Zhong[SUP] 1 3 [/SUP], Lu Zhang[SUP] 5 [/SUP], Peilan Wei[SUP] 4 [/SUP], Shengnan Zhang[SUP] 4 [/SUP], Yuejun Pan[SUP] 1 [/SUP], Yanqun Wang[SUP] 4 [/SUP], Jincun Zhao[SUP] 6 7 [/SUP], Yongjun Guan[SUP] 8 [/SUP], Lei Yu[SUP] 9 10 [/SUP]



Affiliations
Abstract

The protective component of specific memory B cells (MBCs) response relative to serum antibody response in primary SARS-CoV-2 infection is not well understood. Using a relatively unbiased B-cell culture method with a limited number of MBCs in each well (100 cells/well), we characterized the fine specificity of MBC responses against SARS-CoV-2 infection. While serum spike antibody is predominantly against S2 domain, the memory B cells mainly recognize S1 domain. The 44.4-85.3% of S-binding MBCs are specific to S1 domain. High frequency of MBCs (30-62% of SARS-CoV-2 S-specific MBCs) cross-reacting with SARS-CoV S has also been demonstrated. 22-33% of S1-binding MBCs were cross-reactive with the SARS-CoV RBD. In addition, a panel of human monoclonal Ab was derived from S1-binding MBCs recognizing six group epitopes (groups 1-6). Among them, RBD-specific Ab (826) in group 4 and cross-reactive Ab (808) could resist the neutralizing escape of omicron. Herein, we demonstrated that a dominant S1-directed MBC response was generated during primary SARS-CoV-2 infection. More importantly, the cross-reactive RBD-directed MBCs against SARS-CoV may protect against emerging SARS-CoV-2 variants.


 
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