Examining the conditions associated with establishing plasma cell persistence

Plasma cells (PC) produce antigen-specific antibodies following vaccination or infection, playing a vital role in protective immunity. Not all PC have equal lifespans, yet how lifespans are determined remains unknown. Here, we describe a system for the generation of persistent PC in mice following B cell transfer after in vitro activation. We show that PC derived from the donor cells-"induced" PC (iPC)-are detectable for at least 7 wk after transfer, with genetic timestamping revealing some iPC to have persisted for at least 4 wk. In this system, exposure to IL-5 during B cell activation was associated with enhanced seeding of iPC and improved persistence. We further demonstrate that B cell monoclonality for a specificity to which mice are unlikely to be exposed markedly reduced iPC abundance 21 d after transfer compared to polyclonal counterparts, independent of donor B cell expansion, suggesting a role for B cell receptor (BCR) specificity in regulating PC formation or survival. These data support that PC persistence is impacted by conditions at the outset of the immune response, which has implications for the formulation of long-lasting antibody responses. We suggest that the system of in vitro activation and tracking in vivo iPC genesis and subsequent persistence provides a means to identify processes early in B cell activation that are instructive for PC lifespan determination.