Characterization of human FDCs reveals regulation of T cells and antigen presentation to B cells.
Balthasar A HeestersKyah van MegesenIlhan TomrisRobert P de VriesGiuliana MagriHergen SpitsPublished in: The Journal of experimental medicine (2021)
Stromal-derived follicular dendritic cells (FDCs) are essential for germinal centers (GCs), the site where B cells maturate their antibodies. FDCs present native antigen to B cells and maintain a CXCL13 gradient to form the B cell follicle. Yet despite their essential role, the transcriptome of human FDCs remains undefined. Using single-cell RNA sequencing and microarray, we provided the transcriptome of these enigmatic cells as a comprehensive resource. Key genes were validated by flow cytometry and microscopy. Surprisingly, marginal reticular cells (MRCs) rather than FDCs expressed B cell activating factor (BAFF). Furthermore, we found that human FDCs expressed TLR4 and can alter antigen availability in response to pathogen-associated molecular patterns (PAMPs). High expression of PD-L1 and PD-L2 on FDCs activated PD1 on T cells. In addition, we found expression of genes related to T cell regulation, such as HLA-DRA, CD40, and others. These data suggest intimate contact between human FDCs and T cells.
Keyphrases
- single cell
- endothelial cells
- dendritic cells
- induced pluripotent stem cells
- induced apoptosis
- poor prognosis
- rna seq
- genome wide
- pluripotent stem cells
- immune response
- gene expression
- high throughput
- signaling pathway
- toll like receptor
- high resolution
- mass spectrometry
- transcription factor
- machine learning
- oxidative stress
- single molecule
- big data
- electronic health record