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Long-term retention of antigens in germinal centres is controlled by the spatial organisation of the follicular dendritic cell network

Germinal centers (GCs) require sustained availability of antigens to promote antibody affinity maturation against pathogens and vaccines. A key source of antigens for GC B cells are immune complexes (ICs) displayed on follicular dendritic cells (FDCs). Here we show that FDC spatial organization regu...

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Autores principales: Martínez-Riaño, Ana, Wang, Shenshen, Boeing, Stefan, Minoughan, Sophie, Casal, Antonio, Spillane, Katelyn M, Ludewig, Burkhard, Tolar, Pavel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7614842/
https://www.ncbi.nlm.nih.gov/pubmed/37443283
http://dx.doi.org/10.1038/s41590-023-01559-1
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author Martínez-Riaño, Ana
Wang, Shenshen
Boeing, Stefan
Minoughan, Sophie
Casal, Antonio
Spillane, Katelyn M
Ludewig, Burkhard
Tolar, Pavel
author_facet Martínez-Riaño, Ana
Wang, Shenshen
Boeing, Stefan
Minoughan, Sophie
Casal, Antonio
Spillane, Katelyn M
Ludewig, Burkhard
Tolar, Pavel
author_sort Martínez-Riaño, Ana
collection PubMed
description Germinal centers (GCs) require sustained availability of antigens to promote antibody affinity maturation against pathogens and vaccines. A key source of antigens for GC B cells are immune complexes (ICs) displayed on follicular dendritic cells (FDCs). Here we show that FDC spatial organization regulates antigen dynamics in the GC. We identify the existence of a broader FDC heterogeneity within the network. While the entire light zone (LZ) FDC network captures ICs initially, only the central cells of the network function as the antigen reservoir, where different antigens arriving from subsequent immunizations co-localize. Mechanistically, central LZ FDCs constitutively express subtly higher CR2 membrane densities than peripheral LZ FDCs, which strongly increases the IC retention half-life. Even though repeated immunizations gradually saturate central FDCs, B cell responses remain efficient because new antigens partially displace old ones. These results reveal the principles shaping antigen display on FDCs during the GC reaction.
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spelling pubmed-76148422023-08-01 Long-term retention of antigens in germinal centres is controlled by the spatial organisation of the follicular dendritic cell network Martínez-Riaño, Ana Wang, Shenshen Boeing, Stefan Minoughan, Sophie Casal, Antonio Spillane, Katelyn M Ludewig, Burkhard Tolar, Pavel Nat Immunol Article Germinal centers (GCs) require sustained availability of antigens to promote antibody affinity maturation against pathogens and vaccines. A key source of antigens for GC B cells are immune complexes (ICs) displayed on follicular dendritic cells (FDCs). Here we show that FDC spatial organization regulates antigen dynamics in the GC. We identify the existence of a broader FDC heterogeneity within the network. While the entire light zone (LZ) FDC network captures ICs initially, only the central cells of the network function as the antigen reservoir, where different antigens arriving from subsequent immunizations co-localize. Mechanistically, central LZ FDCs constitutively express subtly higher CR2 membrane densities than peripheral LZ FDCs, which strongly increases the IC retention half-life. Even though repeated immunizations gradually saturate central FDCs, B cell responses remain efficient because new antigens partially displace old ones. These results reveal the principles shaping antigen display on FDCs during the GC reaction. 2023-08 2023-07-13 /pmc/articles/PMC7614842/ /pubmed/37443283 http://dx.doi.org/10.1038/s41590-023-01559-1 Text en https://creativecommons.org/licenses/by/4.0/This work is licensed under a CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/) International license.
spellingShingle Article
Martínez-Riaño, Ana
Wang, Shenshen
Boeing, Stefan
Minoughan, Sophie
Casal, Antonio
Spillane, Katelyn M
Ludewig, Burkhard
Tolar, Pavel
Long-term retention of antigens in germinal centres is controlled by the spatial organisation of the follicular dendritic cell network
title Long-term retention of antigens in germinal centres is controlled by the spatial organisation of the follicular dendritic cell network
title_full Long-term retention of antigens in germinal centres is controlled by the spatial organisation of the follicular dendritic cell network
title_fullStr Long-term retention of antigens in germinal centres is controlled by the spatial organisation of the follicular dendritic cell network
title_full_unstemmed Long-term retention of antigens in germinal centres is controlled by the spatial organisation of the follicular dendritic cell network
title_short Long-term retention of antigens in germinal centres is controlled by the spatial organisation of the follicular dendritic cell network
title_sort long-term retention of antigens in germinal centres is controlled by the spatial organisation of the follicular dendritic cell network
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7614842/
https://www.ncbi.nlm.nih.gov/pubmed/37443283
http://dx.doi.org/10.1038/s41590-023-01559-1
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