Heisenberg-Professor University of Munster, Germany Muenster, Nordrhein-Westfalen, Germany
The central nervous system (CNS) is ensheathed by the meninges and cerebrospinal fluid, and recent findings suggest that these CNS-associated border tissues have complex immunological functions. Based on single-cell transcriptomics, we identified a highly location-specific composition and expression of tissue-resident lymphocytes in the meninges, choroid plexus and cerebrospinal fluid. Only the dura layer of the meninges contained a large population of B cells under homeostatic conditions in rodents. These murine dura B cells exhibited long-term tissue residency. In experimental neuroinflammation, B cells exhibited specific tropism for the meninges and their maturation was driven locally by T follicular helper cells. Similar mechanisms were identified in the cerebrospinal fluid and in meningeal preparations in human multiple sclerosis. Surprisingly, the dura also contained B lineage progenitors at the pro-B cell stage typically not found outside of bone marrow, without direct influx from the periphery or the skull bone marrow. We thus identified an unexpected B cell–supporting meningeal microenvironment in the dura locally maintaining neuroinflammation.
