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

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 huma...

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Autores principales: Heesters, Balthasar A., van Megesen, Kyah, Tomris, Ilhan, de Vries, Robert P., Magri, Giuliana, Spits, Hergen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Rockefeller University Press 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8404474/
https://www.ncbi.nlm.nih.gov/pubmed/34424268
http://dx.doi.org/10.1084/jem.20210790
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author Heesters, Balthasar A.
van Megesen, Kyah
Tomris, Ilhan
de Vries, Robert P.
Magri, Giuliana
Spits, Hergen
author_facet Heesters, Balthasar A.
van Megesen, Kyah
Tomris, Ilhan
de Vries, Robert P.
Magri, Giuliana
Spits, Hergen
author_sort Heesters, Balthasar A.
collection PubMed
description 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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spelling pubmed-84044742021-09-01 Characterization of human FDCs reveals regulation of T cells and antigen presentation to B cells Heesters, Balthasar A. van Megesen, Kyah Tomris, Ilhan de Vries, Robert P. Magri, Giuliana Spits, Hergen J Exp Med Technical Advances and Resources 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. Rockefeller University Press 2021-08-23 /pmc/articles/PMC8404474/ /pubmed/34424268 http://dx.doi.org/10.1084/jem.20210790 Text en © 2021 Heesters et al. https://creativecommons.org/licenses/by/4.0/This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/).
spellingShingle Technical Advances and Resources
Heesters, Balthasar A.
van Megesen, Kyah
Tomris, Ilhan
de Vries, Robert P.
Magri, Giuliana
Spits, Hergen
Characterization of human FDCs reveals regulation of T cells and antigen presentation to B cells
title Characterization of human FDCs reveals regulation of T cells and antigen presentation to B cells
title_full Characterization of human FDCs reveals regulation of T cells and antigen presentation to B cells
title_fullStr Characterization of human FDCs reveals regulation of T cells and antigen presentation to B cells
title_full_unstemmed Characterization of human FDCs reveals regulation of T cells and antigen presentation to B cells
title_short Characterization of human FDCs reveals regulation of T cells and antigen presentation to B cells
title_sort characterization of human fdcs reveals regulation of t cells and antigen presentation to b cells
topic Technical Advances and Resources
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8404474/
https://www.ncbi.nlm.nih.gov/pubmed/34424268
http://dx.doi.org/10.1084/jem.20210790
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