Lymphoid origin of a lineage of intrinsically activated plasmacytoid dendritic cell in mice and humans

Abstract

We identified a mouse pDC lineage derived exclusively from the common lymphoid progenitor (CLP) that is dependent on expression of Bcl11a. CLP-derived pDC have a unique gene expression profile that includes hallmark B cell genes not normally expressed in pDCs and therefore we refer to this lineage as “B-pDCs.” Unlike classical pDC, B-pDC express an inherent activation signature, localize preferentially to secondary lymphoid organs and expand more robustly and also induce increased T cell proliferation relative to classical pDCs following Toll-like receptor 9 (TLR9) engagement. B-pDCs lack IFN-α secretion but instead express a distinct cytokine profile and display high levels of the cell-surface receptor tyrosine kinase Axl. Murine B-pDCs represent a CLP-derived DC lineage that is genetically, phenotypically, and functionally homologous to an AXL+ DC subtype recently discovered in human blood1–4.