Commonalities Between pDCs and B Cells

Abstract

Plasmacytoid dendritic cells (pDCs) are a subpopulation of dendritic cells that secrete large amounts of interferons (IFNs) in response to stimuli that activate the Toll-like receptors TLR9 or TLR7. The C-type lectin blood dendritic cell antigen 2 (BDCA2) is uniquely expressed by pDCs, and antibodies that bind BDCA2 inhibit IFN production in response to TLR signaling. Cao et al . found that the abundance of BDCA2 at the cell surface was increased, and signaling was reconstituted in Jurkat cells or a mouse T cell hybridoma cell line when the cells were also transfected to express the γ subunit of the Fcε receptor (FcεR1γ) but not when BDCA2 was coexpressed with the immunoreceptor tyrosine-based activation motif (ITAM) adaptor DAP12 or the related protein DAP10. Analysis of the mRNA and protein abundance of signaling proteins associated with either B cell receptor (BCR) or T cell receptor (TCR) signaling revealed that the signaling cascade of isolated human pDCs most resembled that downstream of BCRs and included the B cell-specific adaptor B cell linker (BLNK, also known as SLP-65 or BASH). Studies with stably transfected human Burkitt lymphoma Namalwa cells (expressing BDCA2, FcεR1γ, and IRF7, a necessary downstream factor) showed that antibody-mediated cross-linking of BDCA2 inhibited IFN production in response to TLR9, TLR7, or TLR8 activation. Thus, BDCA2 appears to use the FcεR1γ as the ITAM adaptor to signal through a BCR-like signaling pathway to mediate inhibition of TLR signaling in pDCs. W. Cao, L. Zhang, D. B. Rosen, L. Bover, G. Watanabe, M. Bao, L. L. Lanier, Y.-J. Liu, BDCA2/FCεRIγ complex signals through a novel BCR-like pathway in human plasmacytoid dendritic cells. PLoS Biol. 5 , e248 (2007). [PubMed]