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


The Journal of Clinical Investigation

Contributing to research themes:

Memory B cells (MBC) can provide a recall response able to supplement waning antibodies with an affinity-matured response better able to neutralise variant viruses. We studied a cohort of elderly care home residents and younger staff (median age 87yrs and 56yrs respectively) who had survived COVID-19 outbreaks with only mild/asymptomatic infection. The cohort was selected to enrich for a high proportion who had lost neutralising antibodies (nAb), to specifically investigate the reserve immunity from SARS-CoV-2-specific MBC in this setting. Class-switched spike and RBD-tetramer-binding MBC persisted five months post-mild/asymptomatic SARS-CoV-2 infection, irrespective of age. The majority of spike/RBD-specific MBC had a classical phenotype but activated memory B cells, that may indicate ongoing antigenic stimulation or inflammation, were expanded in the elderly. Spike/RBD-specific MBC remained detectable in the majority who had lost nAb, although at lower frequencies and with a reduced IgG/IgA isotype ratio. Functional spike/S1/RBD-specific recall was also detectable by ELISpot in some who had lost nAb, but was significantly impaired in the elderly. Our findings demonstrate a reserve of SARS-CoV-2-specific MBC persists beyond loss of nAb, but highlight the need for careful monitoring of functional defects in spike/RBD-specific B cell immunity in the elderly.

Author list:


  1. Division of Infection and Immunity, University College London, London, United Kingdom

  2. Virus Reference Department, Public Health England, London, United Kingdom

  3. Immunisation and Countermeasures Division, Public Health England, London, United Kingdom

  4. Department of Infectious Diseases, King's College London, London, United Kingdom

  5. London Coronavirus Response Cell, Public Health England, London, United Kingdom


Anna Jeffery-Smith,1 Alice R. Burton,1 Sabela Lens,1 Chloe Rees-Spear,1 Jessica Davies,1 Monika Patel,2 Robin Gopal,2 Luke Muir,1 Felicity Aiano,3 Katie J. Doores,4 J. Yimmy Chow,5 Shamez N. Ladhani,3 Maria Zambon,2 Laura E. McCoy,1 and Mala K. Maini.1