PT  - JOURNAL ARTICLE
AU  - Ana Martinez-Riano
AU  - Shenshen Wang
AU  - Stefan Boeing
AU  - Sophie Minoughan
AU  - Antonio Casal
AU  - Katelyn M Spillane
AU  - Burkhard Ludewig
AU  - Pavel Tolar
TI  - Long-term retention of antigens in germinal centres is controlled by the spatial organisation of the follicular dendritic cell network
AID  - 10.1101/2022.09.06.506650
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.09.06.506650
4099  - http://biorxiv.org/content/early/2022/09/07/2022.09.06.506650.short
4100  - http://biorxiv.org/content/early/2022/09/07/2022.09.06.506650.full
AB  - 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 show the existence of two light zone (LZ) FDC populations, which differ in the duration of antigen retention. While the entire light zone (LZ) FDC network captures ICs initially, only the central cells of the network function as a long-term antigen reservoir, where different antigens arriving from subsequent immunizations co-localize. Mechanistically, central FDCs constitutively express subtly higher CR2 membrane densities than peripheral 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.Competing Interest StatementThe authors have declared no competing interest.