Plasmacytoid dendritic cells activate lymphoid-specific genetic programs irrespective of their cellular origin

Immunity. 2004 Jul;21(1):43-53. doi: 10.1016/j.immuni.2004.06.011.

Abstract

The 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 alpha (pTalpha) 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 pTalpha 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 pTalpha 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Bone Marrow Cells / physiology*
  • Cell Differentiation
  • Cell Lineage
  • Dendritic Cells / physiology*
  • Gene Rearrangement, B-Lymphocyte, Heavy Chain
  • Hematopoietic Stem Cells / physiology*
  • Homeodomain Proteins / metabolism
  • Humans
  • Interferon Type I / metabolism
  • Membrane Glycoproteins / metabolism
  • Mice
  • Mice, Transgenic
  • Plasma Cells / physiology*
  • Receptors, Antigen, T-Cell, alpha-beta

Substances

  • Homeodomain Proteins
  • Interferon Type I
  • Membrane Glycoproteins
  • Receptors, Antigen, T-Cell, alpha-beta
  • pre-T cell receptor alpha
  • RAG-1 protein