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Updated: Jan 25, 2026

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Differential transcriptome and development of human peripheral plasma cell subsets.

Swetha Garimalla1, Doan C Nguyen2, Jessica L Halliley3

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Human antibody-secreting cells (ASCs) are diverse, with distinct subsets identified post-vaccination. These diverse ASCs originate from shared precursors and possess long-term survival potential, influencing antibody response longevity.

Keywords:
Adaptive immunityImmunoglobulinsImmunology

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Area of Science:

  • Immunology
  • Cell Biology
  • Vaccinology

Background:

  • Antibody-secreting cells (ASCs) are crucial for adaptive immunity, traditionally defined by CD19loCD38hiCD27hi markers.
  • Variability in vaccine-induced antibody response longevity suggests heterogeneity within ASC populations.

Purpose of the Study:

  • To investigate the heterogeneity of circulating ASCs following vaccination.
  • To characterize distinct ASC subsets based on surface markers, morphology, and molecular profiles.
  • To assess the survival potential and differentiation pathways of these ASC subsets.

Main Methods:

  • Multicolor flow cytometry to identify and quantify ASC subsets.
  • VH repertoire analysis to assess B cell clonality and interconnectivity.
  • RNA transcriptome analysis to delineate molecular differences between subsets.
  • In vitro cell-free system mimicking bone marrow (BM) microniche to test differential survival.

Main Results:

  • Identified 5 circulating ASC subsets (3 CD19+ and 2 CD19-) contributing to vaccine-specific responses.
  • Demonstrated in vivo proliferation and activation across all identified ASC subsets.
  • VH repertoire analysis revealed strong oligoclonality and interconnectivity among ASC subsets and memory B cells.
  • Transcriptome analysis showed distinct molecular profiles for CD19+ and CD19- subsets, involving pathways like cell cycle and TNF-α.
  • All ASC subsets exhibited similar long-term in vitro survival (48 days), indicating inherent long-lived potential.

Conclusions:

  • Vaccine-induced ASCs, despite differing surface markers (CD19, CD138), arise from common proliferative precursors.
  • Distinct transcriptomes differentiate ASC subsets, influencing their functional characteristics.
  • The inherent long-lived potential of all ASC compartments suggests peripheral plasma cell survival is influenced by bone marrow homing and niche interactions.