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<p>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&#xa0;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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年7月1日

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  • 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

摘要

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.