SARS-CoV-2–specific memory B cells can persist in the elderly who have lost detectable neutralizing antibodies

Anna Jeffery-Smith, Alice R. Burton, Sabela Lens, Chloe Rees-Spear, Jessica Davies, Monika Patel, Robin Gopal, Luke Muir, Felicity Aiano, Katie J. Doores, J. Yimmy Chow, Shamez N. Ladhani, Maria Zambon, Laura E. McCoy, Mala K. Maini*

*Corresponding author for this work

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Memory B cells (MBCs) can provide a recall response able to supplement waning antibodies (Abs) with an affinity-matured response better able to neutralize variant viruses. We studied a cohort of elderly care home residents and younger staff (median age of 87 years and 56 years, respectively), who had survived COVID-19 outbreaks with only mild or asymptomatic infection. The cohort was selected because of its high proportion of individuals who had lost neutralizing antibodies (nAbs), thus allowing us to specifically investigate the reserve immunity from SARS-CoV-2–specific MBCs in this setting. Class-switched spike and receptor-binding domain (RBD) tetramer–binding MBCs persisted 5 months after mild or asymptomatic SARS-CoV-2 infection, irrespective of age. The majority of spike- and RBD-specific MBCs had a classical phenotype, but we found that activated MBCs, indicating possible ongoing antigenic stimulation or inflammation, were expanded in the elderly group. Spike- and RBD-specific MBCs remained detectable in the majority of individuals who had lost nAbs, although at lower frequencies and with a reduced IgG/IgA isotype ratio. Functional spike-, S1 subunit of the spike protein– (S1-), and RBD-specific recall was also detectable by enzyme-linked immune absorbent spot (ELISPOT) assay in some individuals who had lost nAbs, but was significantly impaired in the elderly. Our findings demonstrate that a reserve of SARS-CoV-2–specific MBCs persists beyond the loss of nAbs but highlight the need for careful monitoring of functional defects in spike- and RBD-specific B cell immunity in the elderly.

Original languageEnglish
Article number152042
Number of pages13
JournalJournal of Clinical Investigation
Issue number2
Publication statusPublished - 18 Jan 2022

Bibliographical note

Funding Information: This work was supported by PHE and by a Medical College of St. Bartholomew's Hospital Trustees Clinical Research Fellowship (to AJS), and National Institute for Health Research (NIHR) Efficacy and Mechanism Evaluation (EME), EU Horizon 2020, and UK Research and Innovation (UKRI), NIHR UK-CIC grants (to MKM). LEM is supported by a Medical Research Council Career Development Award (MR/R008698/1). Additional support was provided by the UCL Coronavirus Response Fund made possible through generous donations from UCL's supporters, alumni, and friends (to LEM). KJD is supported by the King's Together Rapid COVID-19 Call.

Open Access: This is an open access article published under the terms of the Creative Commons Attribution 4.0 International License.

Publisher Copyright: © 2022, Jeffery-Smith et al.

Citation: Jeffery-Smith, Anna, et al. "SARS-CoV-2–specific memory B cells can persist in the elderly who have lost detectable neutralizing antibodies." The Journal of clinical investigation 132.2 (2022).



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