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

Ana Martínez-Riaño, Shenshen Wang, Stefan Boeing, Sophie Minoughan, Antonio Casal, Katelyn Spillane, Burkhard Ludewig, Pavel Tolar*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)
29 Downloads (Pure)

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.
Original languageEnglish
Pages (from-to)1281-1294
Number of pages14
JournalNature Immunology
Volume24
Issue number8
DOIs
Publication statusPublished - 13 Jul 2023

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