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Affinity-independent memory B cell origin of the early antibody-secreting cell response in naive individuals upon SARS-CoV-2 vaccination

Memory B cells (MBCs) formed over the individual’s lifetime constitute nearly half of the circulating B cell repertoire in humans. These pre-existing MBCs dominate recall responses to their cognate antigens, but how they respond to recognition of novel antigens is not well understood. Here, we track...

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Main Authors: Li, Zhe (Author) , Obraztsova, Anna S. (Author) , Shang, Fuwei (Author) , Oludada, Opeyemi Ernest (Author) , Malapit, Joshua Reginald (Author) , Busch, Katrin (Author) , Straaten, Monique van (Author) , Stebbins, Erec (Author) , Murugan, Rajagopal (Author) , Wardemann, Hedda (Author)
Format: Article (Journal)
Language:English
Published: 10 September 2024
In: Immunity
Year: 2024, Volume: 57, Issue: 9, Pages: 2191-2201.e1-e5
ISSN:1097-4180
DOI:10.1016/j.immuni.2024.07.023
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1016/j.immuni.2024.07.023
Verlag, kostenfrei, Volltext: https://www.sciencedirect.com/science/article/pii/S1074761324003728
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Author Notes:Zhe Li, Anna Obraztsova, Fuwei Shang, Opeyemi Ernest Oludada, Joshua Malapit, Katrin Busch, Monique van Straaten, Erec Stebbins, Rajagopal Murugan, and Hedda Wardemann
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Summary:Memory B cells (MBCs) formed over the individual’s lifetime constitute nearly half of the circulating B cell repertoire in humans. These pre-existing MBCs dominate recall responses to their cognate antigens, but how they respond to recognition of novel antigens is not well understood. Here, we tracked the origin and followed the differentiation paths of MBCs in the early anti-spike (S) response to mRNA vaccination in SARS-CoV-2-naive individuals on single-cell and monoclonal antibody levels. Pre-existing, highly mutated MBCs showed no signs of germinal center re-entry and rapidly developed into mature antibody-secreting cells (ASCs). By contrast, and despite similar levels of S reactivity, naive B cells showed strong signs of antibody affinity maturation before differentiating into MBCs and ASCs. Thus, pre-existing human MBCs differentiate into ASCs in response to novel antigens, but the quality of the humoral and cellular anti-S response improved through the clonal selection and affinity maturation of naive precursors.
Item Description:Online verfügbar: 20. August 2024, Artikelversion: 10. September 2024
Gesehen am 05.03.2025
Physical Description:Online Resource
ISSN:1097-4180
DOI:10.1016/j.immuni.2024.07.023

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