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Characterization of human FDCs reveals regulation of T cells and antigen presentation to B cells
Author(s) -
Balthasar A. Heesters,
Kyah van Megesen,
Ilhan Tomris,
Robert P. de Vries,
Giuliana Magri,
Hergen Spits
Publication year - 2021
Publication title -
the journal of experimental medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 8.483
H-Index - 448
eISSN - 1540-9538
pISSN - 0022-1007
DOI - 10.1084/jem.20210790
Subject(s) - follicular dendritic cells , germinal center , cd40 , microbiology and biotechnology , biology , cxcl13 , b cell , antigen , antigen presenting cell , flow cytometry , antigen presentation , transcriptome , stromal cell , t cell , naive b cell , immunology , immune system , antibody , gene expression , gene , cytotoxic t cell , cancer research , chemokine , chemokine receptor , in vitro , biochemistry
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.

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