Skull bone marrow (BM) has emerged as an important immune interface with the central nervous system (CNS). Park and colleagues identify germinal center-like lymphoid structures within skull BM that can generate adaptive immune responses to CNS-derived antigens and contribute to anti-tumor immunity in experimental glioma. The skull bone marrow (BM) is increasingly recognized as an immune interface with the central nervous system (CNS). Vascular channels and diploic veins connect skull BM with the dura mater, providing routes for the exchange of cells and soluble molecules between these compartments.1,2 Cerebrospinal fluid can access skull BM niches, while skull BM supplies myeloid cells and immature B cells to the meninges and, under some conditions, the CNS parenchyma.3,4,5 Organized lymphoid hubs containing germinal center (GC) B cells have also been identified around meningeal venous plexuses, where they support local humoral immune responses.6 More recently, neuron-derived proteins were shown to accumulate at skull-associated borders, where they are sampled by resident immune cells.7 Despite these anatomical and functional connections, whether skull BM can organize antigen-specific adaptive immune responses to CNS-derived antigens has remained unclear. Park and colleagues now identify GC-like lymphoid structures in skull BM and examine their contribution to CNS immunosurveillance.8 Comparing BM from...