Characterization of human FDCs reveals regulation of T cells and antigen presentation to B cells

J Exp Med. 2021 Oct 4;218(10):e20210790. doi: 10.1084/jem.20210790. Epub 2021 Aug 23.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity
  • Antigen Presentation*
  • Antigen-Presenting Cells / immunology
  • B-Lymphocytes / immunology*
  • B7-H1 Antigen / genetics
  • B7-H1 Antigen / metabolism
  • Dendritic Cells, Follicular / physiology*
  • Gene Expression Profiling
  • Gene Expression Regulation
  • HLA-DR alpha-Chains / genetics
  • Humans
  • Intercellular Signaling Peptides and Proteins / genetics
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Jurkat Cells
  • Programmed Cell Death 1 Ligand 2 Protein / genetics
  • Programmed Cell Death 1 Ligand 2 Protein / metabolism
  • Programmed Cell Death 1 Receptor / metabolism
  • Receptors, Growth Factor / genetics
  • Receptors, Growth Factor / metabolism
  • Toll-Like Receptors / genetics
  • Toll-Like Receptors / metabolism


  • B7-H1 Antigen
  • CD274 protein, human
  • HLA-DR alpha-Chains
  • Intercellular Signaling Peptides and Proteins
  • PDCD1 protein, human
  • PDCD1LG2 protein, human
  • Programmed Cell Death 1 Ligand 2 Protein
  • Programmed Cell Death 1 Receptor
  • Receptors, Growth Factor
  • Toll-Like Receptors