TY - JOUR
T1 - Characterization of human FDCs reveals regulation of T cells and antigen presentation to B cells
AU - Heesters, Balthasar A.
AU - van Megesen, Kyah
AU - Tomris, Ilhan
AU - de Vries, Robert P.
AU - Magri, Giuliana
AU - Spits, Hergen
N1 - Funding Information: This work is supported by an ERC Starting Grant from the European Commission (802780 to R.P. de Vries) and a Dutch Research Council (NWO) ZonMw Veni fellowship (91618032 to B.A. Heesters). Publisher Copyright: © 2021 Heesters et al. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/8/23
Y1 - 2021/8/23
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85114850022&partnerID=8YFLogxK
U2 - https://doi.org/10.1084/jem.20210790
DO - https://doi.org/10.1084/jem.20210790
M3 - Article
C2 - 34424268
SN - 0022-1007
VL - 218
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 10
M1 - e20210790
ER -