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* Multiorgan Transplantation Program, Toronto General Research Institute, Toronto General Hospital,
Ontario Cancer Institute,
Division of Experimental Therapeutics,
University Health Network and Hospital for Sick Children,
¶ Department of Surgery, and
|| Department of Pathology, University of Toronto, Toronto, Ontario, Canada
The developmental biology of dendritic cells (DC) under physiological conditions remains unclear. In this study, we show that mouse CD11c+ MHC class II–lineage– cells are immediate precursors of conventional DC and are widely distributed in both bone marrow and lymphoid tissues. These precursors have a high clonal efficiency, and when cocultured on a supportive stromal monolayer or adoptively transferred in vivo, generate a population CD11c+MHC class II+ DC that retain limited proliferation capacity. During steady state conditions, a small proportion of immediate DC precursors (DCp) and DCs are dividing actively in bone marrow and spleen. Cytokines that initiate and support proliferation of immediate DCp were defined. Collectively, our findings provide evidence of a distinct development pathway for conventional DC in both bone marrow and lymphoid tissues and highlight the importance of in situ replication of immediate DCp and DC in maintaining conventional DC populations.
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