Remodeling of light and dark zone follicular dendritic cells governs germinal center responses

The efficient generation of germinal center (GC) responses requires the directed movement of B cells between distinct microenvironments underpinned by specialized B cell-interacting reticular cells (BRCs). How BRCs are reprogrammed to cater to the developing GC remains unclear and is largely hindered by the incomplete resolution of the cellular composition of the B cell follicle. Here, we utilized the genetic targeting of Cxcl13-expressing cells to define the molecular identity of the BRC landscape. Single-cell transcriptomic analysis revealed that BRC subset specification was predetermined in the primary B cell follicle. Further topological remodeling of light and dark zone follicular dendritic cells required the CXCL12-dependent cross-talk with B cells, and dictated GC output by retaining B cells in the follicle and steering their interaction with follicular helper T cells. Together, our results reveal that poised BRC-defined microenvironments establish a feed-forward system that determines the efficacy of the GC reaction.