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

• Published in: Proceedings of the National Academy of Sciences - PNAS 2017-02, Vol.114 (8), p.1988-1993
• Main Authors: Zhang, Hong, Gregorio, Josh D., Iwahori, Toru, Zhang, Xiangyue, Choi, Okmi, Tolentino, Lorna L., Prestwood, Tyler, Carmi, Yaron, Engleman, Edgar G.
• Format: Article
• Language: English
• Subjects: Biological Sciences; Bone marrow; Cell growth; Dendritic cells; Gene expression; Genotype & phenotype; Lymphocytes; Viral infections
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1610630114

Plasmacytoid dendritic cells (pDCs) are known mainly for their secretion of type I IFN upon viral encounter. We describe a CD2hiCD5⁺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 CD2hiCD5⁺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.