Lymphatic constraint of germinal centers optimizes protective antibody responses

Abstract

Summary Immunization strategies are central to pathogen control, where efficacy relies on antigen distribution and inflammatory context. Lymphatic vessels are necessary conduits for antigen transport that actively remodel in peripheral tissues and draining lymph nodes (LN) in response to their inflammatory context. In the present study, we found that inhibiting viral-induced lymphatic remodeling in skin and LNs prompted germinal center (GC) expansion but, paradoxically, decreased the protective antibody response. Whilst GCs scaled proportionately, larger GCs failed to support proliferative bursts consistent with clonal selection, due to impaired T-B cell interactions. Accordingly, follicle and GC size is evolutionarily conserved across diverse mammals despite increased LN size. Lymphatic vessels controlled GC size through two coordinated processes: lymphatic remodeling in infected skin limited viral transport to the LN, while the resulting permissive environment in the LN supported perifollicular lymphangiogenesis that constrained GC expansion.