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

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

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

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

U-Th-Pb Dating of Monazite by Single-Collector ICP-MS: Pitfalls and Potential

Methods are presented for in situ determination of Pb/U, Pb/Th, and Pb/Pb ages in monazite by laser ablation, single-collector, magnetic sector inductively coupled plasma-mass spectrometry (ICP-MS). Analytical precisions for individual spot analyses are ±2–3% for 206Pb/238U and 207Pb/235U, 4% for 208Pb/232Th, and 1–2% for 207Pb/206Pb (2σ, SD). For pooled analyses these precisions are ∼ ± 1–2% for 206Pb/238U, 207Pb/235U, and 208Pb/232Th and ≤1% for 207Pb/206Pb (2σ, SE). When normalized to Trebilcock, LA-ICP-MS ages on other monazite standards can deviate from their thermal ionization mass spectrometry (ID-TIMS) ages by up to 1% for 207Pb/206Pb and up to 5% for 206Pb/238U, 207Pb/235U, and 208Pb/232Th ages. This variability has also been observed for secondary ion mass spectrometry (SIMS) Th-Pb dating. The source(s) of these inaccuracies remains unknown. Although there are significant uncertainties inherent in this technique, U-Th-Pb monazite dating by LA-ICP-MS has important applications where this higher level of uncertainty is acceptable. Application to a large vein monazite from the Llallagua tin district of Bolivia suggests mineralization at 17–21 Ma, consistent with 21 Ma K-Ar ages from wallrock minerals but distinct from ∼45 Ma ages from apatite (Sm/Nd) and zircon (Pb/Pb)