Convergent differentiation: myeloid and lymphoid pathways to murine plasmacytoid dendritic cells.
The developmental origin of IFN-producing plasmacytoid dendritic cells (pDCs) has been uncertain. In the present study, we tracked the development of pDCs in cultures of BM precursors stimulated with Flt3 ligand. Common myeloid precursors (CMPs) produced both conventional DCs (cDCs) and pDCs via the DC-restricted common DC precursor. Common lymphoid precursors (CLPs) produced only a few cDCs with variable efficiency, but produced pDCs via a transient intermediate precursor with B-cell potential. The pDCs of both origins produced IFN-α when stimulated with CpG oligonucleotides. The pDCs of CLP origin showed evidence of past RAG1 expression and had D-J rearrangements in IgH genes. Most pDCs and all cDCs of CMP origin lacked these signs of a lymphoid past. However, in these cultures, some pDCs of CMP origin showed evidence of past RAG1 expression and had D-J IgH gene rearrangements; most of these derived from a subset of CMPs already expressing RAG1.
The Walter and Eliza Hall Institute, Parkville, Australia.
Priyanka
P
Sathe
David
D
Vremec
Li
L
Wu
Lynn
L
Corcoran
Ken
K
Shortman
D019264:Adoptive Transfer; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000378:metabolism; D001854:Bone Marrow Cells / Q000145:classification / Q000166:cytology / Q000378:metabolism; D019070:Cell Lineage; D002469:Cell Separation; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D002999:Clone Cells / Q000166:cytology / Q000378:metabolism; D018899:CpG Islands; D003713:Dendritic Cells / Q000166:cytology* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics; D016130:Immunophenotyping; D016898:Interferon-alpha / Q000096:biosynthesis / Q000235:genetics; D038041:Lymphopoiesis / Q000235:genetics / Q000502:physiology*; D008565:Membrane Proteins / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D038042:Myelopoiesis / Q000235:genetics / Q000502:physiology*; D009841:Oligonucleotides / Q000494:pharmacology; D011828:Radiation Chimera; D013047:Specific Pathogen-Free Organisms
D018398:Homeodomain Proteins; D016898:Interferon-alpha; D008565:Membrane Proteins; D009841:Oligonucleotides; C084881:flt3 ligand protein; C064658:RAG-1 protein