Organized immunity in the CNS: what stroke reveals about neuroinflammation and lymphoid niches

Organized adaptive immunity can emerge in the CNS under specific inflammatory and stromal conditions. The study by Yang et al. in this issue of the JCI reports that experimental ischemic stroke induced germinal center-like B cell follicles through microglial MIF-CD74/CXCR4 signaling and in situ B cell proliferation, promoting chronic neuroinflammation. These findings align with a growing body of evidence that the brain and meninges can support ectopic lymphoid structures in multiple sclerosis, during aging, and in certain gliomas. This Commentary integrates these observations to highlight shared principles, disease-specific outcomes, and unresolved questions regarding the identity and function of lymphoid aggregates in the CNS.