Booster vaccination improves the durability of antibody-secreting plasma cells
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Booster vaccination can restore antibody titres and protection, but whether it improves long-term durability by expanding plasma cell (PC) numbers or also by shifting PC fate toward intrinsically longer-lived states remains unclear. Here we established longitudinal in vivo ground truth for PC persistence by combining PC-specific genetic timestamping, clonal tracking, and multi-timepoint single-cell profiling across spleen and bone marrow. We resolved PC longevity as a layered, non-binary architecture comprising short-, intermediate-, and long-lived programs, and showed that program identity is specified early in secondary lymphoid tissues and largely maintained as PCs populate bone marrow niches. Primary vaccine responses initiated from naïve B-cells generated a prominent intermediate-lived wave, whereas memory B-cell recall during boosting redistributed output toward long-lived programs rather than recreating the intermediate-lived compartment characteristic of priming. Conserved longevity signatures projected onto early circulating PCs provide a cross-species framework to infer durability programs, supporting benchmarking of vaccine regimens by predicted persistence rather than peak titres.
Highlights
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Genetic timestamping resolves short-, intermediate-, and long-lived PC programs
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Longevity programs are imprinted early and maintained from lymphoid organs to bone marrow
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Cross-species signatures stratify human blood and bone marrow PCs by persistence
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Boosting via MBC recall enriches long-lived PC and contracts the intermediate-lived tier
