BDCA-2, BDCA-3, and BDCA-4: Three Markers for Distinct Subsets of Dendritic Cells in Human Peripheral Blood

Abstract

We have generated a panel of mAbs that identify three presumably novel human dendritic cell Ags: BDCA-2, BDCA-3, and BDCA-4. In blood, BDCA-2 and BDCA-4 are expressed on CD11c− CD123bright plasmacytoid dendritic cells, whereas BDCA-3 is expressed on small population of CD11c+ CD123− dendritic cells. All three Ags are not detectable on a third blood dendritic cell population, which is CD1c+ CD11cbright CD123dim, or on any other cells in blood. BDCA-4 is also expressed on monocyte-derived and CD34+ cell-derived dendritic cells. Expression of all three Ags dramatically changes once blood dendritic cells undergo in vitro maturation. BDCA-2 is completely down-regulated on plasmacytoid CD11c− CD123bright dendritic cells, expression of BDCA-3 is up-regulated on both plasmacytoid CD11c− CD123bright dendritic cells and CD1c+ CD11cbright CD123dim dendritic cells, and expression of BDCA-4 is up-regulated on CD1c+ CD11cbright CD123dim dendritic cells. BDCA-2 is rapidly internalized at 37°C after mAb labeling. The three presumably novel Ags serve as specific markers for the respective subpopulations of blood dendritic cells in fresh blood and will be of great value for their further analysis and to evaluate their therapeutic potential.

Induction of interferon‐α production in plasmacytoid dendritic cells by immune complexes containing nucleic acid released by necrotic or late apoptotic cells and lupus IgG

“…This was done by enriching for BDCA-4-positive cells, known to correspond to NIPC/PDCs (44). The effectiveness of the enrichment was determined by flow cytometry after staining for BDCA-2, also selectively expressed on NIPC/PDCs (44). The purity of the BDCA-4-enriched fraction was between 40% and 45%, while the original PBMCs contained ϳ0.5% BDCA-4-positive cells (data not shown).…”

“…Therefore, we investigated whether these cells also produced IFN␣ in response to apoptotic or necrotic cells, combined with SLE IgG. This was done by enriching for BDCA-4-positive cells, known to correspond to NIPC/PDCs (44). The effectiveness of the enrichment was determined by flow cytometry after staining for BDCA-2, also selectively expressed on NIPC/PDCs (44).…”

The type I interferon system in systemic lupus erythematosus

“…NIPCs/PDCs are infrequent in the circulation (Ͻ1% of peripheral blood mononuclear cells [PBMCs]) and can be recruited to sites of inflammation. The cells express, for instance, class II major histocompatibility complex (MHC), CD4, CD40, CD83, high levels of the IL-3 receptor (CD123), and 2 specific markers termed blood dendritic cell antigen 2 (BDCA-2) and BDCA-4, but lack the costimulatory molecules CD80 and CD86 (17,18). The BDCA-2 molecule represents an endocytic type II C-type lectin, which might function as an antigen-capturing molecule (19).…”

Inactivation of the EGF‐TM7 receptor EMR4 after the Pan‐Homo divergence

“…On DC, mouse EMR4, like the murine homologue of EMR1, F4/80, is mainly expressed by the CD8 -cells, which are considered to represent myeloid DC [23]. To investigate whether transcriptional regulation has been conserved in human EMR4, we examined transcription of EGF-TM7 receptors in human blood DC subsets, defined by the expression of blood DC antigen (BDCA) markers [24]. Whereas BDCA-1 and BDCA-3 are expressed on myeloid DC, BDCA-4 is expressed on plasmacytoid DC that are likely of lymphoid origin.…”

“…Blood DC of the myeloid and plasmacytoid lineage were isolated from human PBMC according to the protocol of Dzionek et al [24]. In short, after depletion of CD19 + B cells using anti-CD19 microbeads (Miltenyi Biotec, Bergisch Gladbach, Germany), cells were labeled with PE-conjugated mAb directed against BDCA-1, BDCA-3 or BDCA-4 for 15 min at 4°C in FcR-blocking reagents (Miltenyi Biotec).…”