Brain-border immune hubs: skull bone marrow hosts germinal-center–like niches that surveil the CNS and boost anti-tumor immunity

A study reveals the skull bone marrow harbors organized, germinal center–like lymphoid structures with follicular helper T cells that promote B cell activation and humoral responses to CNS-derived antigens. Brain-derived antigens reach these skull niches via glymphatic routes, enabling local antigen presentation, T/B cell interactions, clonal B cell expansion and somatic hypermutation. In mouse brain tumor models, skull BM responses contribute to anti-tumor immunity and can function independently of traditional secondary lymphoid organs; local CD40 agonism combined with IL-21 and IFN-γ enhances skull B cell activity and IgG responses, boosting intratumoral immunity and survival. The findings position skull bone marrow as a CNS border immunosurveillance site with potential relevance to human brain immunity and therapy.