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Human memory B cells show plasticity and adopt multiple fates upon recall response to SARS-CoV-2.

ABSTRACT: The B cell response to different pathogens uses tailored effector mechanisms and results in functionally specialized memory B (B_m) cell subsets, including CD21⁺ resting, CD21^-CD27⁺ activated and CD21^-CD27^- B_m cells. The interrelatedness between these B_m cell subsets remains unknown. Here we showed that single severe acute respiratory syndrome coronavirus 2-specific B_m cell clones showed plasticity upon antigen rechallenge in previously exposed individuals. CD21^- B_m cells were the predominant subsets during acute infection and early after severe acute respiratory syndrome coronavirus 2-specific immunization. At months 6 and 12 post-infection, CD21⁺ resting B_m cells were the major B_m cell subset in the circulation and were also detected in peripheral lymphoid organs, where they carried tissue residency markers. Tracking of individual B cell clones by B cell receptor sequencing revealed that previously fated B_m cell clones could redifferentiate upon antigen rechallenge into other B_m cell subsets, including CD21^-CD27^- B_m cells, demonstrating that single B_m cell clones can adopt functionally different trajectories.

SUBMITTER: Zurbuchen Y

PROVIDER: S-EPMC10232369 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature

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Human memory B cells show plasticity and adopt multiple fates upon recall response to SARS-CoV-2.

Zurbuchen Yves Y Michler Jan J Taeschler Patrick P Adamo Sarah S Cervia Carlo C Raeber Miro E ME Acar Ilhan E IE Nilsson Jakob J Warnatz Klaus K Soyka Michael B MB Moor Andreas E AE Boyman Onur O

Nature immunology 20230427 6

The B cell response to different pathogens uses tailored effector mechanisms and results in functionally specialized memory B (Bm) cell subsets, including CD21+ resting, CD21-CD27+ activated and CD21-CD27- Bm cells. The interrelatedness between these Bm cell subsets remains unknown. Here we showed that single severe acute respiratory syndrome coronavirus 2-specific Bm cell clones showed plasticity ...[more]

PMID: 37106039

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Project description:As of March 2022, there have been over 450 million reported SARS-CoV-2 cases worldwide, and more than 4 billion people have received their primary series of a COVID-19 vaccine. In order to longitudinally track SARS-CoV-2 antibody levels in people after vaccination or infection, a large-scale COVID-19 sero-surveillance progam entitled SPARTA (SeroPrevalence and Respiratory Tract Assessment) was established early in the pandemic. Anti-RBD antibody levels were tracked in more than 1,000 people. There was no significant decrease in antibody levels during the first 14 months after infection in unvaccinated participants, however, significant waning of antibody levels was observed following vaccination, regardless of previous infection status. Moreover, participants who were pre-immune to SARS-CoV-2 prior to vaccination seroconverted to significantly higher antibody levels, and antibodies were maintained at significantly higher levels than in previously infected, unvaccinated participants. This pattern was entirely due to differences in the magnitude of the initial seroconversion event, and the rate of antibody waning was not significantly different based on the pre-immune status. Participants who received a third (booster) dose of an mRNA vaccine not only increased their anti-RBD antibody levels ∼14-fold, but they also had ∼3 times more anti-RBD antibodies compared to the peak of their antibody levels after receiving their primary vaccine series. In order to ascertain whether the presence of serum antibodies is important for long-term seroprotection, PBMCs from 13 participants who lost all detectable circulating antibodies after vaccination or infection were differentiated into memory cells in vitro . There was a significant recall of memory B cells in the absence of serum antibodies in 70% of the vaccinated participants, but not in any of the infected participants. Therefore, there is a strong connection between anti-RBD antibody levels and the effectiveness of memory B cell recall.

Dataset Information

Human memory B cells show plasticity and adopt multiple fates upon recall response to SARS-CoV-2.

Publications

Human memory B cells show plasticity and adopt multiple fates upon recall response to SARS-CoV-2.

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