High-dimensional spectral flow cytometry reveals distinct fates of SARS-CoV-2-specific adaptive immune cells during memory formation

High-dimensional spectral flow cytometry reveals distinct fates of SARS-CoV-2-specific adaptive immune cells during memory formation
Immunological memory is a hallmark of adaptive immunity and allows an accelerated and enhanced immune response upon re-infection with the same pathogen. We investigated the antigen-specific adaptive immune memory formation in a longitudinal cohort of COVID-19 patients during acute infection to 12 months into recovery using spectral flow cytometry combined with cellular indexing of transcriptomes and T and B cell receptor sequencing.

Focusing on the memory B cell formation upon SARS-CoV-2 infection, our approach revealed that single clones of SARS-CoV-2-specific MBCs followed multiple fates with distinctive phenotypic and functional characteristics. 6–12 months after infection, most circulating MBCs were CD21+ resting cells, which also accumulated in peripheral lymphoid organs where they acquired markers of tissue residency. Conversely, at acute infection and following SARS-CoV-2-specific immunization, CD21– MBCs became the predominant subsets, with atypical MBCs expressing high T-bet, inhibitory molecules, and distinct chemokine receptors. B cell receptor sequencing allowed tracking of individual MBC clones differentiating into CD21+, CD21–CD27+, and CD21–CD27– cell fates. Collectively, single MBC clones can adopt functionally different trajectories, thus contributing to immunity to infection.