SARS-CoV-2–specific memory B cells can persist in the elderly who have lost detectable neutralizing antibodies
Anna Jeffery-Smith, … , Laura E. McCoy, Mala K. Maini
Anna Jeffery-Smith, … , Laura E. McCoy, Mala K. Maini
Published November 29, 2021
Citation Information: J Clin Invest. 2022;132(2):e152042. https://doi.org/10.1172/JCI152042.
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Research Article Immunology

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

Abstract

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.

Authors

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

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Figure 3

Preserved memory phenotype but skewed isotype of spike- and RBD-specific B cells with loss of nAbs.

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Preserved memory phenotype but skewed isotype of spike- and RBD-specific...
(A) Representative FACS plots of IgM/IgG on spike-specific, RBD-specific, and global MBCs from an infected individual. (B) Frequency of IgG+, IgA+ (IgD–IgG–IgM–), and IgM+ spike–specific MBCs by nAbs (n = 17) and no nAbs (n = 18) at 5 months and staff (gray, n = 10) and resident (blue, n = 25) status. (C) Frequency of IgG+, IgA+, and IgM+ RBD–specific MBCs by nAbs (n = 11) and no nAbs (n = 7) at 5 months and by staff (gray, n = 6) and resident (blue, n = 12) status. (D) Representative FACS plots of CD21 and CD27 on spike-specific, RBD-specific, and global MBCs from an infected individual. (E) Frequency of CD21–CD27+, CD21+CD27+, and CD21–CD27– subsets of spike-specific MBCs by nAbs (n = 17) and no nAbs (n = 19) at 5 months, ordered by increasing age. (F) Frequency of CD21–CD27+, CD21+CD27+, and CD21–CD27– subsets of RBD-specific MBCs with nAbs (n = 13) or no nAbs (n = 8) at 5 months, ordered by increasing age. (G) Frequency of CD21–CD27+ RBD-specific MBCs by nAbs (n = 13) and no nAbs (n = 8) at 5 months and by staff (gray, n = 7) and resident (blue, n = 14) status. (H) Representative plots and summary data showing the frequency of spike-specific and global MBCs expressing T-bet, by nAbs (n = 19) and no nAbs (n = 13) at 5 months, by staff (gray, n = 10) and resident (blue, n = 22) status, and by uninfected controls (n = 13). (B, C, and G) Bars indicate the median and IQR. A Mann-Whitney U test was used to determine statistical significance (*P < 0.05, **P < 0.005). (B) IgG P = 0.0382; NS, IgA P = 0.0045; NS, IgM. (C) IgG P = 0.0220; NS, IgA P = 0.0055; NS, IgM. (G) NS, P = 0.0180. (H) Bars indicate the median and IQR. Statistical significance was assessed by Kruskal-Wallis test with Dunn’s correction between nAb, no nAb, and uninfected subgroups and staff, resident, and uninfected subgroups, respectively, on global cell populations (all NS). Analysis was performed on all individuals with 50 or more cells in the parent gate for all phenotypic analyses.