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Maturation and persistence of the anti-SARS-CoV-2 memory B cell response

Aurélien Sokal, Pascal Chappert, Anais Roeser, Giovanna Barba-Spaeth, Slim Fourati, Imane Azzaoui, Alexis Vandenberghe, Ignacio Fernandez, Magali Bouvier-Alias, Etienne Crickx, Asma Beldi Ferchiou, Sophie Hue, Laetitia Languille, Samia Baloul, France Noizat-Pirenne, Marine Luka, Jérôme Megret, Mickaël Ménager, Jean-Michel Pawlotsky, Simon Fillatreau, Felix A Rey, Jean-Claude Weill, Claude-Agnès Reynaud, Matthieu Mahévas
doi: https://doi.org/10.1101/2020.11.17.385252
Aurélien Sokal
1Institut Necker Enfants Malades (INEM), INSERM U1151/CNRS UMS 8253, Université de Paris, Paris, France
2Service de Médecine Interne, Centre Hospitalier Universitaire Henri-Mondor, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Paris-Est Créteil (UPEC), Créteil, France
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Pascal Chappert
1Institut Necker Enfants Malades (INEM), INSERM U1151/CNRS UMS 8253, Université de Paris, Paris, France
3Inovarion, Paris, France
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Anais Roeser
1Institut Necker Enfants Malades (INEM), INSERM U1151/CNRS UMS 8253, Université de Paris, Paris, France
2Service de Médecine Interne, Centre Hospitalier Universitaire Henri-Mondor, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Paris-Est Créteil (UPEC), Créteil, France
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Giovanna Barba-Spaeth
4Institut Pasteur, Unité de Virologie Structurale, Paris, France
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Slim Fourati
5Département de Virologie, Bactériologie, Hygiène et Mycologie-Parasitologie, Centre Hospitalier Universitaire Henri-Mondor, Assistance Publique-Hôpitaux de Paris (AP-HP), Créteil, France
6INSERM U955, équipe 18. Institut Mondor de Recherche Biomédicale (IMRB), Université Paris-Est Créteil (UPEC), Créteil, France
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Imane Azzaoui
2Service de Médecine Interne, Centre Hospitalier Universitaire Henri-Mondor, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Paris-Est Créteil (UPEC), Créteil, France
7INSERM U955, équipe 2. Institut Mondor de Recherche Biomédicale (IMRB), Université Paris-Est Créteil (UPEC), Créteil, France
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Alexis Vandenberghe
2Service de Médecine Interne, Centre Hospitalier Universitaire Henri-Mondor, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Paris-Est Créteil (UPEC), Créteil, France
7INSERM U955, équipe 2. Institut Mondor de Recherche Biomédicale (IMRB), Université Paris-Est Créteil (UPEC), Créteil, France
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Ignacio Fernandez
4Institut Pasteur, Unité de Virologie Structurale, Paris, France
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Magali Bouvier-Alias
5Département de Virologie, Bactériologie, Hygiène et Mycologie-Parasitologie, Centre Hospitalier Universitaire Henri-Mondor, Assistance Publique-Hôpitaux de Paris (AP-HP), Créteil, France
6INSERM U955, équipe 18. Institut Mondor de Recherche Biomédicale (IMRB), Université Paris-Est Créteil (UPEC), Créteil, France
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Etienne Crickx
1Institut Necker Enfants Malades (INEM), INSERM U1151/CNRS UMS 8253, Université de Paris, Paris, France
2Service de Médecine Interne, Centre Hospitalier Universitaire Henri-Mondor, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Paris-Est Créteil (UPEC), Créteil, France
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Asma Beldi Ferchiou
8Département Immunologie-Hématologie, Centre Hospitalier Universitaire Henri-Mondor, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Paris-Est Créteil (UPEC), 94000, Créteil, France
9INSERM U955, équipe immunorégulation et biothérapie (I-BIOT) Institut Mondor de Recherche Biomédicale (IMRB), Université Paris-Est Créteil (UPEC), Créteil, France
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Sophie Hue
8Département Immunologie-Hématologie, Centre Hospitalier Universitaire Henri-Mondor, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Paris-Est Créteil (UPEC), 94000, Créteil, France
10Institut de Recherche Vaccinale (VRI), Université Paris-Est Créteil (UPEC), Faculté de Médecine, Créteil, France
11INSERM U955, équipe 16. Institut Mondor de Recherche Biomédicale (IMRB), Université Paris-Est Créteil (UPEC), Créteil, France
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Laetitia Languille
2Service de Médecine Interne, Centre Hospitalier Universitaire Henri-Mondor, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Paris-Est Créteil (UPEC), Créteil, France
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Samia Baloul
12Département de Santé Publique, Unité de Recherche Clinique (URC), CEpiA (Clinical Epidemiology and Ageing), EA 7376-Institut Mondor de Recherche Biomédicale (IMRB), Centre Hospitalier Universitaire Henri-Mondor, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Paris-Est Créteil (UPEC), Créteil, France
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France Noizat-Pirenne
13Etablissement Français du Sang, INSERM U955, Université Paris-Est Créteil (UPEC), Créteil, France
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Marine Luka
14Réponses inflammatoires et réseaux transcriptomiques dans les maladies, Institut Imagine, INSERM UMR1163, ATIP-Avenir Team, Université de Paris, Paris, France
15Labtech Single-cell@Imagine, Institut Imagine, INSERM UMR 1163, Paris, France
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Jérôme Megret
16Plateforme de Cytométrie en Flux, Structure Fédérative de Recherche Necker, INSERM US24-CNRS UMS3633, Paris, France
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Mickaël Ménager
14Réponses inflammatoires et réseaux transcriptomiques dans les maladies, Institut Imagine, INSERM UMR1163, ATIP-Avenir Team, Université de Paris, Paris, France
15Labtech Single-cell@Imagine, Institut Imagine, INSERM UMR 1163, Paris, France
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Jean-Michel Pawlotsky
5Département de Virologie, Bactériologie, Hygiène et Mycologie-Parasitologie, Centre Hospitalier Universitaire Henri-Mondor, Assistance Publique-Hôpitaux de Paris (AP-HP), Créteil, France
6INSERM U955, équipe 18. Institut Mondor de Recherche Biomédicale (IMRB), Université Paris-Est Créteil (UPEC), Créteil, France
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Simon Fillatreau
1Institut Necker Enfants Malades (INEM), INSERM U1151/CNRS UMS 8253, Université de Paris, Paris, France
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Felix A Rey
4Institut Pasteur, Unité de Virologie Structurale, Paris, France
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Jean-Claude Weill
1Institut Necker Enfants Malades (INEM), INSERM U1151/CNRS UMS 8253, Université de Paris, Paris, France
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  • For correspondence: claude-agnes.reynaud@inserm.fr jean-claude.weill@inserm.fr matthieu.mahevas@aphp.fr
Claude-Agnès Reynaud
1Institut Necker Enfants Malades (INEM), INSERM U1151/CNRS UMS 8253, Université de Paris, Paris, France
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  • For correspondence: claude-agnes.reynaud@inserm.fr jean-claude.weill@inserm.fr matthieu.mahevas@aphp.fr
Matthieu Mahévas
1Institut Necker Enfants Malades (INEM), INSERM U1151/CNRS UMS 8253, Université de Paris, Paris, France
2Service de Médecine Interne, Centre Hospitalier Universitaire Henri-Mondor, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Paris-Est Créteil (UPEC), Créteil, France
7INSERM U955, équipe 2. Institut Mondor de Recherche Biomédicale (IMRB), Université Paris-Est Créteil (UPEC), Créteil, France
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  • For correspondence: claude-agnes.reynaud@inserm.fr jean-claude.weill@inserm.fr matthieu.mahevas@aphp.fr
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Abstract

Memory B cells play a fundamental role in host defenses against viruses, but to date, their role have been relatively unsettled in the context of SARS-CoV-2. We report here a longitudinal single-cell and repertoire profiling of the B cell response up to 6 months in mild and severe COVID-19 patients. Distinct SARS-CoV-2 Spike-specific activated B cell clones fueled an early antibody-secreting cell burst as well as a durable synchronous germinal center response. While highly mutated memory B cells, including preexisting cross-reactive seasonal Betacoronavirus-specific clones, were recruited early in the response, neutralizing SARS-CoV-2 RBD-specific clones accumulated with time and largely contributed to the late remarkably stable memory B-cell pool. Highlighting germinal center maturation, these cells displayed clear accumulation of somatic mutations in their variable region genes over time. Overall, these findings demonstrate that an antigen-driven activation persisted and matured up to 6 months after SARS-CoV-2 infection and may provide long-term protection.

Competing Interest Statement

M.M. received research funds from GSK, outside of the submitted work and personal fees from LFB and Amgen, outside of the submitted work. JC.W. received consulting fees from Merieux, outside of the submitted work. JM.P. received personal fees from Abbvie, Gilead, Merck, and Siemens Healthcare, outside the submitted work.

Footnotes

  • ↵† shared senior authorship

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Maturation and persistence of the anti-SARS-CoV-2 memory B cell response
Aurélien Sokal, Pascal Chappert, Anais Roeser, Giovanna Barba-Spaeth, Slim Fourati, Imane Azzaoui, Alexis Vandenberghe, Ignacio Fernandez, Magali Bouvier-Alias, Etienne Crickx, Asma Beldi Ferchiou, Sophie Hue, Laetitia Languille, Samia Baloul, France Noizat-Pirenne, Marine Luka, Jérôme Megret, Mickaël Ménager, Jean-Michel Pawlotsky, Simon Fillatreau, Felix A Rey, Jean-Claude Weill, Claude-Agnès Reynaud, Matthieu Mahévas
bioRxiv 2020.11.17.385252; doi: https://doi.org/10.1101/2020.11.17.385252
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Maturation and persistence of the anti-SARS-CoV-2 memory B cell response
Aurélien Sokal, Pascal Chappert, Anais Roeser, Giovanna Barba-Spaeth, Slim Fourati, Imane Azzaoui, Alexis Vandenberghe, Ignacio Fernandez, Magali Bouvier-Alias, Etienne Crickx, Asma Beldi Ferchiou, Sophie Hue, Laetitia Languille, Samia Baloul, France Noizat-Pirenne, Marine Luka, Jérôme Megret, Mickaël Ménager, Jean-Michel Pawlotsky, Simon Fillatreau, Felix A Rey, Jean-Claude Weill, Claude-Agnès Reynaud, Matthieu Mahévas
bioRxiv 2020.11.17.385252; doi: https://doi.org/10.1101/2020.11.17.385252

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