A distinct subset of plasmacytoid dendritic cells induces activation and differentiation of B and T lymphocytes

Plasmacytoid dendritic cells (pDCs) are known mainly for their secretion of type I IFN upon viral encounter. We describe a CD2^hiCD5⁺CD81⁺ pDC subset, distinguished by prominent dendrites and a mature phenotype, in human blood, bone marrow, and tonsil, which can be generated from CD34⁺ progenitors. These CD2^hiCD5⁺CD81⁺ cells express classical pDC markers, as well as the toll-like receptors that enable conventional pDCs to respond to viral infection. However, their gene expression profile is distinct, and they produce little or no type I IFN upon stimulation with CpG oligonucleotides, likely due to their diminished expression of IFN regulatory factor 7. A similar population of CD5⁺CD81⁺ pDCs is present in mice and also does not produce type I IFN after CpG stimulation. In contrast to conventional CD5^-CD81^- pDCs, human CD5⁺CD81⁺ pDCs are potent stimulators of B-cell activation and antibody production and strong inducers of T-cell proliferation and Treg formation. These findings reveal the presence of a discrete pDC population that does not produce type I IFN and yet mediates important immune functions previously attributed to all pDCs.