Plasmacytoid dendritic cell development

Interferon-producing plasmacytoid dendritic cells (pDC) are a specialized branch of the dendritic cell (DC) family, and their differentiation in mice is closely linked to that of conventional DC (cDC). Several different developmental pathways retain the potential to form pDC and are likely to contribute to the steady-state pDC population. A lymphoid pathway to DC development produces mainly pDC as a branch otherwise leading to B-cell development; such pDC may carry relics of a lymphoid past such as DJ rearrangements of immunoglobulin heavy chain (IgH) genes. The myeloid pathway to pDC and cDC is better known, but recent reassessment has revealed several substreams of development with separate DC-committed precursors. One substream has a lymphoid-like aspect, involving a precursor expressing RAG-1 and producing pDC with IgH gene rearrangements. Another more biased to cDC production produces pDC without such IgH gene rearrangements. Finally, there is the production of interferon-producing pDC-like cells that are not pDC but appear to be cDC precursors; these do not express key pDC markers such as CCR9. Initiation of the DC and then the pDC developmental program overrides any surface marker-expressed developmental bias to other myeloid or lymphoid lineages, resulting in an apparent convergent differentiation to the pDC form. A DC fate is sometimes imprinted early in development, upstream of identifiable myeloid, or lymphoid precursors. This suggests that DC, including pDC, represent a distinct hematopoietic lineage separate from conventional myeloid or lymphoid cells.