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Multimodal single-cell analysis following SARS-CoV-2 breakthrough infection reveals distinct B cell populations

Graus, L. T. M.; Guerra, D.; Chrysostomou, A.; Kerster, G.; van der Straten, K.; van Rijswijk, J.; Tejjani, K.; Beaumont, T.; Bree, G. J.; Sanders, R. W.; van Gils, M. J.; Claireaux, M.

2025-10-31 immunology
10.1101/2025.10.30.685644 bioRxiv
Show abstract

B cells are crucial to mediating durable immunity by generating high-affinity, antigen-specific antibodies and memory B cells upon pathogen exposure and re-exposure. While advances in single-cell technologies have expanded the understanding of B cell heterogeneity, the precise developmental trajectories and functional roles of memory B cell subsets remain poorly characterized. This study employs single-cell RNA sequencing to analyze B cell responses after SARS-CoV-2 re-exposure. The integration of B cell gene expression, surface protein profiles, antigen specificity, and BCR repertoire data from 12 individuals vaccinated against COVID-19 and subsequently infected with SARS-CoV-2 variants reveals dynamic transitions between B cell populations, from activated states to more quiescent phases. Furthermore, the profiling of key surface proteins and mRNA markers enhances the knowledge of B cell-mediated immunity following antigen exposure.

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