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

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...

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Main Authors: Xiaomin Xing, Zhaoyong Zhang, Yingfen Wen, Wenjing Guo, Xulei Zhang, Yuyi Min, Kexin Zhong, Lu Zhang, Peilan Wei, Shengnan Zhang, Yuejun Pan, Yanqun Wang, Jincun Zhao, Yongjun Guan, Lei Yu
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-025-06847-4
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Summary: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.
ISSN:2045-2322