The meningeal B cells: ontogeny, crosstalk, and therapeutic reprogramming at the brain border

The meninges have emerged as a critical immune interface connecting the central nervous system (CNS) with peripheral compartments. Although traditionally viewed as a passive barrier, this compartment contains diverse immune populations, among which B cells have gained attention as key regulators of CNS-associated immunity. Meningeal B cells comprise diverse developmental and functional states shaped by skull bone marrow, peripheral circulation, and mucosal signals. These cells acquire distinct functional states, including antibody production, antigen presentation, and cytokine-mediated regulation, participating in both immune surveillance and pathological inflammation. Beyond intrinsic functions, they coordinate multicellular interactions with T cells, myeloid cells, stromal networks, and vascular, lymphatic, and neural elements at the CNS border. Here, we review their origins, organization, functional diversity, network roles, and strategies for monitoring and therapeutically targeting these states. Understanding how these context-dependent states are organized at CNS borders may provide new insights into immune regulation and precision intervention in neuroinflammatory disorders.