Abstract
The B cell response to different pathogens uses tailored effector mechanisms and results in functionally specialized memory B (B(m)) cell subsets, including CD21(+) resting, CD21(-)CD27(+) activated and CD21(-)CD27(-) B(m) cells. The interrelatedness between these B(m) cell subsets remains unknown. Here we showed that single severe acute respiratory syndrome coronavirus 2-specific B(m) cell clones showed plasticity upon antigen rechallenge in previously exposed individuals. CD21(-) B(m) cells were the predominant subsets during acute infection and early after severe acute respiratory syndrome coronavirus 2-specific immunization. At months 6 and 12 post-infection, CD21(+) resting B(m) cells were the major B(m) cell subset in the circulation and were also detected in peripheral lymphoid organs, where they carried tissue residency markers. Tracking of individual B cell clones by B cell receptor sequencing revealed that previously fated B(m) cell clones could redifferentiate upon antigen rechallenge into other B(m) cell subsets, including CD21(-)CD27(-) B(m) cells, demonstrating that single B(m) cell clones can adopt functionally different trajectories.