Differential transcriptome and development of human peripheral plasma cell subsets

JCI Insight. 2019 May 2;4(9):e126732. doi: 10.1172/jci.insight.126732.

Abstract

Human antibody-secreting cells (ASCs) triggered by immunization are globally recognized as CD19loCD38hiCD27hi. Yet, different vaccines give rise to antibody responses of different longevity, suggesting ASC populations are heterogeneous. We define circulating-ASC heterogeneity in vaccine responses using multicolor flow cytometry, morphology, VH repertoire, and RNA transcriptome analysis. We also tested differential survival using a human cell-free system that mimics the bone marrow (BM) microniche. In peripheral blood, we identified 3 CD19+ and 2 CD19- ASC subsets. All subsets contributed to the vaccine-specific responses and were characterized by in vivo proliferation and activation. The VH repertoire demonstrated strong oligoclonality with extensive interconnectivity among the 5 subsets and switched memory B cells. Transcriptome analysis showed separation of CD19+ and CD19- subsets that included pathways such as cell cycle, hypoxia, TNF-α, and unfolded protein response. They also demonstrated similar long-term in vitro survival after 48 days. In summary, vaccine-induced ASCs with different surface markers (CD19 and CD138) are derived from shared proliferative precursors yet express distinctive transcriptomes. Equal survival indicates that all ASC compartments are endowed with long-lived potential. Accordingly, in vivo survival of peripheral long-lived plasma cells may be determined in part by their homing and residence in the BM microniche.

Keywords: Adaptive immunity; Immunoglobulins; Immunology.

Publication types

  • Research Support, American Recovery and Reinvestment Act
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Antibody Formation
  • Antibody-Producing Cells / immunology*
  • Antigens, CD19 / immunology
  • B-Lymphocytes / immunology
  • Bone Marrow / immunology
  • Bone Marrow Cells / immunology
  • Female
  • Humans
  • Immunization
  • Immunoglobulin G
  • Kinetics
  • Male
  • Middle Aged
  • Phenotype
  • Plasma Cells / immunology*
  • Tetanus / immunology
  • Transcriptome*
  • Vaccination
  • Young Adult

Substances

  • Antigens, CD19
  • Immunoglobulin G