Abstract
AbstractThe magnitude and quality of the germinal center (GC) response decline with age, resulting in poor vaccine-induced immunity in older individuals. A functional GC requires the co-ordination of multiple cell types across time and space, in particular across its two functionally distinct compartments: the light and dark zones. In aged mice, there is CXCR4-mediated mislocalization of T follicular helper (TFH) cells to the dark zone and a compressed network of follicular dendritic cells (FDCs) in the light zone. Here we show that TFH cell localization is critical for the quality of the antibody response and for the expansion of the FDC network upon immunization. The smaller GC and compressed FDC network in aged mice were corrected by provision of TFH cells that colocalize with FDCs using CXCR5. This demonstrates that the age-dependent defects in the GC response are reversible and shows that TFH cells support stromal cell responses to vaccines.
Funder
RCUK | Biotechnology and Biological Sciences Research Council
EC | Horizon 2020 Framework Programme
A*STAR | Science and Engineering Research Council
Wellcome Trust
Department of Health | National Health and Medical Research Council
Deutsche Forschungsgemeinschaft
EC | EC Seventh Framework Programm | FP7 Coordination of Non-Community Research Programmes
Agence Nationale de la Recherche
Publisher
Springer Science and Business Media LLC
Subject
Immunology,Immunology and Allergy
Cited by
31 articles.
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