Novel markers of plasmacytoid dendritic cells
| Molecule . | Nature . | Labeling in plasmacytoid dendritic cells . | Expression in other white cell types . | Comments . |
|---|---|---|---|---|
| Transcription regulators | ||||
| BCL11A | Zinc finger protein | Nuclear (stronger than B cells) | B cells | Detected previously at the RNA and protein level in murine and human pDCs8,17 and shown to be overexpressed by gene-expression profiling in human pDC neoplasms107 |
| E47/E12 (E2A gene products) | Basic helix-loop-helix (bHLH) protein | Nuclear | Most B cells | E47 expression detected at the mRNA level in murine pDCs8 Not previously studied as an immunocytochemical marker of human pDCs |
| FOXP1 | Forkhead protein | Nuclear | Mantle zone B cells Minority of germinal center B cells | Plays a role in transcriptional regulation of B-cell development.108 Not previously studied in the context of human pDCs |
| ICSBP/IRF8 | Interferon regulatory factor | Nuclear | Most B cellsMacrophages | Detected at the RNA level in murine pDCs.8,85 ICSBP-deficient mice display loss of pDCs, which can be restored by enforced ICSBP expression.109-111 Shown to be overexpressed by gene-expression profiling in human pDC neoplasms.107 Not previously studied as an immunocytochemical marker of human pDCs |
| IRF7 | Interferon regulatory factor | Cytoplasmic | Absent | Detected in human pDCs at RNA and protein level (flow cytometry).112-114 Plays an essential role in mice in induction of type 1 IFN production upon virus infection.115 Stimulation of human pDCs with CpG DNA induces activation of NF-κ B and p38 MAPK via TLR9 signaling and leads to the de novo expression of IRF7116 |
| PU.1 | Member of the ETS family | Weak nuclear staining in minority of cells | Most B cellsMacrophages | Detected at mRNA level in murine pDCs.8 The closely related factor Spi.B is detectable at mRNA level in human and murine pDCs and is required for murine pDC development.8,117 Spi.B dependency for murine pDC development has not yet been shown. Not previously studied as an immunocytochemical marker of human pDCs |
| Signaling molecules | ||||
| BLNK (SLP65) | Adapter protein | Cytoplasmic | Most B cells | Phosphorylated in the course of signaling initiated by CD303 (BDCA-2).96 Not previously studied in the context of normal pDCs but shown to be overexpressed by gene-expression profiling in human pDC neoplasms107 |
| Btk | Kinase | Cytoplasmic | Most B cells | Has a negative regulatory effect on murine dendritic cells.118 BTK-deficient dendritic cells in humans show an impaired response to TLR8 signaling.119 Normal numbers of pDCs reported in children lacking the BTK gene.120 Not previously studied as an immunocytochemical marker in human pDCs |
| CD2AP | Adaptor protein | Cytoplasmic | Mantle zone B cells in some samples (very weak) | Not previously studied in the context of pDCs |
| DAP12 (KARAP) | Adaptor protein | Cytoplasmic | Germinal center macrophages, scattered cells in interfollicular areas | Involved in signaling in pDCs initiated via TLR9 and Siglec-H.121-123 Not previously studied as an immunocytochemical marker in human pDCs |
| IRAK1 | Kinase | Membrane and cytoplasmic | Scattered cells in germinal center and interfollicular areas. Probable plasma cells | Involved in signaling induced by interleukin-1, Toll-like receptors, and tumor necrosis factor receptor (TNFR) superfamily molecules linking to the IRF7 transcription factor.124 Not previously studied as an immunocytochemical marker in human pDCs |
| LIME | Trans-membrane adaptor molecule | Cytoplasmic | Most T cellsPlasma cells94 | Not previously studied in the context of pDCs |
| Lyn | Kinase | Cytoplasmic | Most B cellsMyeloid cells125 | Plays a role in the generation and maturation of murine dendritic cells (pDCs not specifically studied).126 Not previously studied as an immunocytochemical marker in human pDCs |
| PLCγ 2 | Phospho-lipase | Weak cytoplasmic staining (compared to B cells) | Most B cells125 | Not previously studied as an immunocytochemical marker in human pDCs |
| Syk | Kinase | Cytoplasmic | Most B cellsMyeloid cells125 | Cross-linking of ILT7/FcϵRI complexes or CD303 (BDCA-2) on pDCs causes phosphorylation of Syk.95,96,127 Not previously studied as an immunocytochemical marker in human pDCs |
| TBC1D4/AS160 | GTPase-activating protein | Cytoplasmic | Many cells in germinal centers | Key regulator of intracellular vescicular trafficking.128 Involved in insulin-induced signaling and phosphorylated by Akt kinase.129 High mRNA levels reported in T cells of patients with atopic dermatitis.130 Not previously studied as an immunocytochemical marker of human pDCs |
| Toll-like receptors: TLR7 and TLR9 | Endosome associated | Cytoplasmic | Some cells in germinal centers, in interfollicular areas, and in plasma cells | These intracellular receptors have been extensively studied as initiators of signaling in murine pDCs.21,81,131,132 Highly expressed in human pDCs.133 Viral binding may initially be mediated by antibodies recognized by Fc receptors before sensing by TLR7.134 Detected at the mRNA level in murine pDCs.8 Not previously studied as immunocytochemical markers in human pDCs |
| Cell surface molecules: CD79b | Associated with surface Ig | Cytoplasmic (weak) | Most B cells, but mantle zone cells stronger than germinal center cells | Detected at the mRNA level in murine pDCs.8 Not previously studied in the context of human pDCs |
| Molecule . | Nature . | Labeling in plasmacytoid dendritic cells . | Expression in other white cell types . | Comments . |
|---|---|---|---|---|
| Transcription regulators | ||||
| BCL11A | Zinc finger protein | Nuclear (stronger than B cells) | B cells | Detected previously at the RNA and protein level in murine and human pDCs8,17 and shown to be overexpressed by gene-expression profiling in human pDC neoplasms107 |
| E47/E12 (E2A gene products) | Basic helix-loop-helix (bHLH) protein | Nuclear | Most B cells | E47 expression detected at the mRNA level in murine pDCs8 Not previously studied as an immunocytochemical marker of human pDCs |
| FOXP1 | Forkhead protein | Nuclear | Mantle zone B cells Minority of germinal center B cells | Plays a role in transcriptional regulation of B-cell development.108 Not previously studied in the context of human pDCs |
| ICSBP/IRF8 | Interferon regulatory factor | Nuclear | Most B cellsMacrophages | Detected at the RNA level in murine pDCs.8,85 ICSBP-deficient mice display loss of pDCs, which can be restored by enforced ICSBP expression.109-111 Shown to be overexpressed by gene-expression profiling in human pDC neoplasms.107 Not previously studied as an immunocytochemical marker of human pDCs |
| IRF7 | Interferon regulatory factor | Cytoplasmic | Absent | Detected in human pDCs at RNA and protein level (flow cytometry).112-114 Plays an essential role in mice in induction of type 1 IFN production upon virus infection.115 Stimulation of human pDCs with CpG DNA induces activation of NF-κ B and p38 MAPK via TLR9 signaling and leads to the de novo expression of IRF7116 |
| PU.1 | Member of the ETS family | Weak nuclear staining in minority of cells | Most B cellsMacrophages | Detected at mRNA level in murine pDCs.8 The closely related factor Spi.B is detectable at mRNA level in human and murine pDCs and is required for murine pDC development.8,117 Spi.B dependency for murine pDC development has not yet been shown. Not previously studied as an immunocytochemical marker of human pDCs |
| Signaling molecules | ||||
| BLNK (SLP65) | Adapter protein | Cytoplasmic | Most B cells | Phosphorylated in the course of signaling initiated by CD303 (BDCA-2).96 Not previously studied in the context of normal pDCs but shown to be overexpressed by gene-expression profiling in human pDC neoplasms107 |
| Btk | Kinase | Cytoplasmic | Most B cells | Has a negative regulatory effect on murine dendritic cells.118 BTK-deficient dendritic cells in humans show an impaired response to TLR8 signaling.119 Normal numbers of pDCs reported in children lacking the BTK gene.120 Not previously studied as an immunocytochemical marker in human pDCs |
| CD2AP | Adaptor protein | Cytoplasmic | Mantle zone B cells in some samples (very weak) | Not previously studied in the context of pDCs |
| DAP12 (KARAP) | Adaptor protein | Cytoplasmic | Germinal center macrophages, scattered cells in interfollicular areas | Involved in signaling in pDCs initiated via TLR9 and Siglec-H.121-123 Not previously studied as an immunocytochemical marker in human pDCs |
| IRAK1 | Kinase | Membrane and cytoplasmic | Scattered cells in germinal center and interfollicular areas. Probable plasma cells | Involved in signaling induced by interleukin-1, Toll-like receptors, and tumor necrosis factor receptor (TNFR) superfamily molecules linking to the IRF7 transcription factor.124 Not previously studied as an immunocytochemical marker in human pDCs |
| LIME | Trans-membrane adaptor molecule | Cytoplasmic | Most T cellsPlasma cells94 | Not previously studied in the context of pDCs |
| Lyn | Kinase | Cytoplasmic | Most B cellsMyeloid cells125 | Plays a role in the generation and maturation of murine dendritic cells (pDCs not specifically studied).126 Not previously studied as an immunocytochemical marker in human pDCs |
| PLCγ 2 | Phospho-lipase | Weak cytoplasmic staining (compared to B cells) | Most B cells125 | Not previously studied as an immunocytochemical marker in human pDCs |
| Syk | Kinase | Cytoplasmic | Most B cellsMyeloid cells125 | Cross-linking of ILT7/FcϵRI complexes or CD303 (BDCA-2) on pDCs causes phosphorylation of Syk.95,96,127 Not previously studied as an immunocytochemical marker in human pDCs |
| TBC1D4/AS160 | GTPase-activating protein | Cytoplasmic | Many cells in germinal centers | Key regulator of intracellular vescicular trafficking.128 Involved in insulin-induced signaling and phosphorylated by Akt kinase.129 High mRNA levels reported in T cells of patients with atopic dermatitis.130 Not previously studied as an immunocytochemical marker of human pDCs |
| Toll-like receptors: TLR7 and TLR9 | Endosome associated | Cytoplasmic | Some cells in germinal centers, in interfollicular areas, and in plasma cells | These intracellular receptors have been extensively studied as initiators of signaling in murine pDCs.21,81,131,132 Highly expressed in human pDCs.133 Viral binding may initially be mediated by antibodies recognized by Fc receptors before sensing by TLR7.134 Detected at the mRNA level in murine pDCs.8 Not previously studied as immunocytochemical markers in human pDCs |
| Cell surface molecules: CD79b | Associated with surface Ig | Cytoplasmic (weak) | Most B cells, but mantle zone cells stronger than germinal center cells | Detected at the mRNA level in murine pDCs.8 Not previously studied in the context of human pDCs |