Plasmacytoid Dendritic Cells Activate Lymphoid-Specific Genetic Programs Irrespective of Their Cellular Origin

AbstractThe developmental origin of type I interferon (IFN)-producing plasmacytoid dendritic cells (PDCs) is controversial. In particular, the rearrangement of immunoglobulin heavy chain (IgH) genes in murine PDCs and the expression of pre-T cell receptor α (pTα) gene by human PDCs were proposed as evidence for their “lymphoid” origin. Here we demonstrate that PDCs capable of IFN production develop efficiently from both myeloid- and lymphoid-committed progenitors. Rearranged IgH genes as well as RAG transcripts were found in both myeloid- and lymphoid-derived PDCs. The human pTα transgenic reporter was activated in both myeloid- and lymphoid-derived PDCs at a level comparable to pre-T cells. PDCs were the only cell population that activated murine RAG1 knockin and human pTα transgenic reporters outside the lymphoid lineage. These results highlight a unique developmental program of PDCs that distinguishes them from other cell types including conventional dendritic cells