Spatial dysregulation of T follicular helper cells impairs vaccine responses in aging

The 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 (T(FH)) cells to the dark zone and a compressed network of follicular dendritic cells (FDCs) in the light zone. Here we show that T(FH) 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 T(FH) cells that colocalize with FDCs using CXCR5. This demonstrates that the age-dependent defects in the GC response are reversible and shows that T(FH) cells support stromal cell responses to vaccines.