Booster vaccination improves the durability of antibody-secreting plasma cells

2026 · doi:10.64898/2026.04.18.719387
preprint OA: closed
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Booster vaccination, by recruiting memory B cells, shifts plasma cell longevity programs toward intrinsically longer-lived states, enhancing durability compared to primary responses.

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The study investigated whether booster vaccination improves the long-term durability of antibody responses by expanding plasma cell numbers and/or by shifting plasma cells toward intrinsically longer-lived fate states. Using longitudinal in vivo plasma-cell genetic timestamping, clonal tracking, and multi-timepoint single-cell profiling across spleen and bone marrow, the authors modeled plasma cell longevity as a layered, non-binary set of short-, intermediate-, and long-lived programs, with program identity specified early and largely maintained after bone-marrow niche occupation. They found that primary vaccination from naïve B cells produced a prominent intermediate-lived plasma cell wave, while boosting via memory B-cell recall redistributed output toward long-lived programs rather than restoring the intermediate-lived compartment seen during priming. A key limitation acknowledged is that longevity programs were inferred from program identity and signatures across models/timepoints rather than measured as direct “ground truth” for every possible regimen and context. This paper does not explicitly discuss endometriosis or adenomyosis; it was included in the corpus via a keyword match in the upstream search index.

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Abstract

Summary 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 Genetic timestamping resolves short-, intermediate-, and long-lived PC programs Longevity programs are imprinted early and maintained from lymphoid organs to bone marrow Cross-species signatures stratify human blood and bone marrow PCs by persistence Boosting via MBC recall enriches long-lived PC and contracts the intermediate-lived tier
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Summary 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 Genetic timestamping resolves short-, intermediate-, and long-lived PC programs Longevity programs are imprinted early and maintained from lymphoid organs to bone marrow Cross-species signatures stratify human blood and bone marrow PCs by persistence Boosting via MBC recall enriches long-lived PC and contracts the intermediate-lived tier Competing Interest Statement D.P.C. is named inventor on a patent relating to synthetic lethality of NMT inhibitors in high-MYC cancers (WO2020128475); D.P.C. and M.S.H. are named inventors on a patent relating to Follicular Lymphoma biomarker signature (GB2509744.5). D.P.C. Research funding - AstraZeneca and Boehringer Ingelheim. These competing interests are unrelated to this work. All other authors declare no competing interests.

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