This Opinion deals with the apparent paradox between the ‘immune privileged' status of the central nervous system (CNS) and its propensity to act as a B-cell fostering environment in a variety of neurological disorders. Evidence will be reviewed that: (i) molecules regulating B-cell homing and survival are produced in the CNS, (ii) in different neuroinflammatory diseases, B cells can undergo a local recapitulation of the differentiation occurring in secondary lymphoid organs and (iii) ectopic lymphoid follicles develop in the meninges of multiple sclerosis (MS) patients.