LAUSR

Significance During infection, antibodies are produced to target the rapid clearance of initial pathogen with high-affinity variants used long term to protect against reinfection. Under the guidance of CD4 T cell regulation, different subtypes of antibodies emerge expressing separable molecular clearance mechanisms. Here, we study the transcriptional programs imprinted upon vaccine-induced single isotype-specific plasma cells specialized for early short-lived antibody production, long-term production of high-affinity antibodies, and splenic plasma cells persistent at steady state. We reveal divergent transcriptional programs across these phases of adaptive immunity and between antibody isotype that differentially influence pathways for antibody production, intercellular communication, cellular homing, and longevity. Understanding the cellular distribution of these molecular differences will help target and enhance isotype-specific immune effector outcomes through vaccination.