BDCA2/Fc epsilon RI gamma complex signals through a novel BCR-like pathway in human plasmacytoid dendritic cells

PLoS Biol. 2007 Sep 11;5(10):e248. doi: 10.1371/journal.pbio.0050248.

Abstract

Dendritic cells are equipped with lectin receptors to sense the extracellular environment and modulate cellular responses. Human plasmacytoid dendritic cells (pDCs) uniquely express blood dendritic cell antigen 2 (BDCA2) protein, a C-type lectin lacking an identifiable signaling motif. We demonstrate here that BDCA2 forms a complex with the transmembrane adapter Fc epsilon RI gamma. Through pathway analysis, we identified a comprehensive signaling machinery in human pDCs, similar to that which operates downstream of the B cell receptor (BCR), which is distinct from the system involved in T cell receptor (TCR) signaling. BDCA2 crosslinking resulted in the activation of the BCR-like cascade, which potently suppressed the ability of pDCs to produce type I interferon and other cytokines in response to Toll-like receptor ligands. Therefore, by associating with Fc epsilon RI gamma, BDCA2 activates a novel BCR-like signaling pathway to regulate the immune functions of pDCs.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / immunology
  • Animals
  • B-Lymphocytes / immunology
  • Dendritic Cells / immunology*
  • Humans
  • Interferon Type I / immunology
  • Jurkat Cells
  • Lectins, C-Type / genetics
  • Lectins, C-Type / immunology*
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / immunology*
  • Mice
  • Multiprotein Complexes / immunology
  • NF-kappa B / immunology
  • Oligonucleotide Array Sequence Analysis
  • Receptors, Antigen, B-Cell / genetics
  • Receptors, Antigen, B-Cell / immunology*
  • Receptors, IgE / genetics
  • Receptors, IgE / immunology*
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / immunology*
  • Signal Transduction / physiology*

Substances

  • Adaptor Proteins, Signal Transducing
  • B cell linker protein
  • CLEC4C protein, human
  • Interferon Type I
  • Lectins, C-Type
  • Membrane Glycoproteins
  • Multiprotein Complexes
  • NF-kappa B
  • Receptors, Antigen, B-Cell
  • Receptors, IgE
  • Receptors, Immunologic