Monocytes and lymphoid tissue DCs of various subsets arise from a common progenitor known as the macrophage and DC precursor (MDP) in the bone marrow. To become a classical splenic DC (cDC), development is then thought to proceed via a common DC precursor (CDP), which is restricted to producing cDCs and plasmacytoid DCs (pDCs), and a dedicated cDC precursor (pre-cDC), which differentiates into cDCs in lymphoid organs. In keeping with this scheme, MDPs and CDPs could be detected in mouse bone marrow but not the blood and spleen, and pre-cDCs were found in all these sites, as well as the lymph nodes. Adoptive transfer of pre-cDCs confirmed their propensity to become cDCs. Experiments with parabiotic mice (which are surgically joined so that they share a blood circulation) led the authors to conclude that pre-cDCs arise in the bone marrow, travel through the blood to peripheral lymphoid organs, where they become cDCs.
Imaging of fluorescent-protein-expressing pre-cDCs in the lymph nodes revealed that they initially (1–5 hours after transfer) tend to be sessile and positioned close to high endothelial venules. They then (16–18 hours after transfer) develop a more migratory behaviour, becoming distributed throughout the lymph node paracortex, and obtain a dendritic morphology; both are features that are characteristic of DCs. Final differentiation of cDCs was also associated with gain of proliferative capacity. This was shown to be controlled by regulatory T cells (as depletion of regulatory T cells led to increased division of pre-cDCs and cDCs in the lymph nodes under steady state conditions) and to involve the FLT3 (FMS-related tyrosine kinase 3) pathway.
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