Long-term retention of antigens in germinal centers is controlled by the spatial organization of the follicular dendritic cell network
File(s)Martinez et al accepted version.pdf (107.47 MB)
Accepted version
Author(s)
Type
Journal Article
Abstract
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 heterogeneity within the FDC 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 colocalize. 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.
Date Issued
2023-08-01
Date Acceptance
2023-06-13
Citation
Nature Immunology, 2023, 24 (8), pp.1281-1294
ISSN
1529-2908
Publisher
Nature Research
Start Page
1281
End Page
1294
Journal / Book Title
Nature Immunology
Volume
24
Issue
8
Copyright Statement
Copyright © 2023 Springer-Verlag. This version of the article has been accepted for publication, after peer review (when applicable) and is subject to Springer Nature’s AM terms of use, but is not the Version of Record and does not reflect post-acceptance improvements, or any corrections. The Version of Record is available online at: http://dx.doi.org/10.1038/s41590-023-01559-1
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/37443283
PII: 10.1038/s41590-023-01559-1
Subjects
ANTIBODY
B-CELLS
COMPLEMENT-DEPENDENT TRANSPORT
EXPRESSION
GENERATION
IMMUNE-COMPLEXES
Immunology
Life Sciences & Biomedicine
LYMPHOTOXIN
RECEPTOR
Science & Technology
STROMAL CELLS
TUMOR-NECROSIS-FACTOR
Publication Status
Published
Coverage Spatial
United States
Date Publish Online
2023-07-13