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.
Zurbuchen, Yves