Antigen transmission by replicating antigen-bearing dendritic cells.
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.
Diao
Jun
J
Toronto General Hospital Research Institute, University Health Network, University of Toronto, Ontario, Canada.
Winter
Erin
E
Chen
Wenhao
W
Xu
Feng
F
Cattral
Mark S
MS
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D000941:Antigens / Q000276:immunology; D002455:Cell Division; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology*; D049452:Green Fluorescent Proteins / Q000032:analysis / Q000235:genetics; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D008863:Microspheres; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
D000941:Antigens; D049452:Green Fluorescent Proteins