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During convalescence, antibodies are subjected to affinity maturation, which enhances the antibody binding strength and generates new specificities that neutralize virus variants. Here, we performed a single\u2010cell RNA sequencing analysis of spike\u2010specific B cells from a SARS\u2010CoV\u20102 convalescent subject. After COVID\u201019 vaccination, matured infection\u2010induced MBC underwent recall and differentiated into plasmablasts. Furthermore, the transcriptomic profiles of newly activated B cells transiently shifted toward the ones of atypical and CXCR3\n                    <jats:sup>+<\/jats:sup>\n                    B cells and several B\u2010cell clonotypes massively expanded. We expressed monoclonal antibodies (mAbs) from all B\u2010cell clones from the largest clonotype that used the VH3\u201053 gene segment. The\n                    <jats:italic>in vitro<\/jats:italic>\n                    analysis revealed that some somatic hypermutations enhanced the neutralization breadth of mAbs in a putatively stochastic manner. Thus, somatic hypermutation of B\u2010cell clonotypes generates an anticipatory memory that can neutralize new virus variants.\n                  <\/jats:p>","DOI":"10.1002\/eji.202451056","type":"journal-article","created":{"date-parts":[[2024,4,9]],"date-time":"2024-04-09T15:14:24Z","timestamp":1712675664000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Diversification of the VH3\u201053 immunoglobulin gene segment by somatic hypermutation results in neutralization of SARS\u2010CoV\u20102 virus variants"],"prefix":"10.1002","volume":"54","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-2748-4080","authenticated-orcid":false,"given":"Matthias","family":"Bruhn","sequence":"first","affiliation":[{"name":"Institute for Experimental Infection Research TWINCORE, Centre for Experimental and Clinical Infection Research a joint venture between the Helmholtz Centre for Infection Research and the Hannover Medical School  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maureen","family":"Obara","sequence":"additional","affiliation":[{"name":"Institute for Experimental Infection Research TWINCORE, Centre for Experimental and Clinical Infection Research a joint venture between the Helmholtz Centre for Infection Research and the Hannover Medical School  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdus","family":"Salam","sequence":"additional","affiliation":[{"name":"Institute for Experimental Infection Research TWINCORE, Centre for Experimental and Clinical Infection Research a joint venture between the Helmholtz Centre for Infection Research and the Hannover Medical School  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bibiana","family":"Costa","sequence":"additional","affiliation":[{"name":"Institute for Experimental Infection Research TWINCORE, Centre for Experimental and Clinical Infection Research a joint venture between the Helmholtz Centre for Infection Research and the Hannover Medical School  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annett","family":"Ziegler","sequence":"additional","affiliation":[{"name":"Institute for Experimental Infection Research TWINCORE, Centre for Experimental and Clinical Infection Research a joint venture between the Helmholtz Centre for Infection Research and the Hannover Medical School  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inken","family":"Waltl","sequence":"additional","affiliation":[{"name":"Institute for Experimental Infection Research TWINCORE, Centre for Experimental and Clinical Infection Research a joint venture between the Helmholtz Centre for Infection Research and the Hannover Medical School  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Pavlou","sequence":"additional","affiliation":[{"name":"Institute for Experimental Infection Research TWINCORE, Centre for Experimental and Clinical Infection Research a joint venture between the Helmholtz Centre for Infection Research and the Hannover Medical School  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Hoffmann","sequence":"additional","affiliation":[{"name":"Infection Biology Unit German Primate Center  G\u00f6ttingen Germany"},{"name":"Faculty of Biology Georg\u2010August\u2010University G\u00f6ttingen  G\u00f6ttingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theresa","family":"Graalmann","sequence":"additional","affiliation":[{"name":"Department for Rheumatology and Immunology Hannover Medical School  Hannover Germany"},{"name":"Junior Research Group for Translational Immunology TWINCORE, Centre 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Hospital Harvard Medical School  Boston Massachusetts USA"},{"name":"German Center for Infection Research (DZIF) partner site Hannover\u2010Braunschweig Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrich","family":"Kalinke","sequence":"additional","affiliation":[{"name":"Institute for Experimental Infection Research TWINCORE, Centre for Experimental and Clinical Infection Research a joint venture between the Helmholtz Centre for Infection Research and the Hannover Medical School  Hannover Germany"},{"name":"German Center for Infection Research (DZIF) partner site Hannover\u2010Braunschweig Hannover Germany"},{"name":"Cluster of Excellence RESIST (EXC 2155) Hannover Medical School  Hannover 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