Mapping the pathways of development of the specialized DC subtypes
The haematopoietic pathways leading to the development of the different dendritic cell (DC) subtypes are beginning to be mapped. Earlier work from this and other laboratories indicated that both myeloid and lymphoid restricted precursor cells from bone marrow had a capacity to produce the range of DC subtypes found in a tissue such as spleen, pointing to a surprising developmental flexibility at this stage. We have since isolated two downstream precursor cells, a “pro-DC” (or common DC precursor) committed to producing all the DC subtypes found in spleen, but not other haematopoietic cells, and further downstream a “pre-DC” committed to forming the conventional DC subtypes found in spleen, but not the spleen plasmacytoid DC subtype. We have developed a culture system which models these developmental pathways leading to spleen-type DC, and use this to perform true clonal analysis of DC development from these precursor cells. Currently we are examining the developmental relationship between the precursor cells which produce DC and those which produce macrophages. In addition, we are mapping two distinct routes for the formation of plasmacytoid DC.