Sci. STKE, 6 November 2007
Immunology Commonalities Between pDCs and B Cells
Nancy R. Gough
Science's STKE, AAAS, Washington, DC 20005, USA
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 subunit of the Fc receptor (FcR1) 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, FcR1, 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 FcR1 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/FCRI complex signals through a novel BCR-like pathway in human plasmacytoid dendritic cells. PLoS Biol. 5, e248 (2007). [PubMed]
Citation: N. R. Gough, Commonalities Between pDCs and B Cells. Sci. STKE 2007, tw404 (2007).
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