Antigen transmission by replicating antigen-bearing dendritic cells

J Immunol. 2007 Sep 1;179(5):2713-21. doi: 10.4049/jimmunol.179.5.2713.

Abstract

During steady-state conditions, conventional spleen dendritic cells (DC) turn over every 2-3 days. Recent evidence indicates that in situ proliferation of DC arising from immediate conventional DC precursors is an important contributor to their homeostasis. In this study, we report that replication-competent conventional DC precursors and DC can internalize and transfer model particulate and soluble Ags directly to their DC progeny during cell division. Real-time confocal microscopy and flow cytometry indicated that Ag transmission to progeny was symmetrical, and suggested that other mechanisms of inter-DC Ag transfer were not involved. Soluble protein Ags inherited by DC progeny were presented effectively to Ag-specific T lymphocytes. Furthermore, we show that the number of DC, and the proportion that are actively proliferating, expands several-fold during an immune response against a viral infection. Our results point to an unanticipated mechanism in which DC are continuously replaced from Ag-bearing replication-competent precursor cells that pass Ag molecules onto their progeny through successive cell divisions. Our findings help explain how Ag may persist in a population of DC despite the brief lifespan of individual mature DC.

MeSH terms

  • Animals
  • Antigen Presentation / immunology*
  • Antigens / immunology
  • Cell Division*
  • Dendritic Cells / cytology*
  • Dendritic Cells / immunology*
  • Green Fluorescent Proteins / analysis
  • Green Fluorescent Proteins / genetics
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Microscopy, Confocal
  • Microspheres
  • Spleen / immunology
  • T-Lymphocytes / immunology

Substances

  • Antigens
  • Green Fluorescent Proteins