Single-cell profiling of CNS border compartment leukocytes reveals that B cells and their progenitors reside in non-diseased meninges

• Published in: Nature neuroscience Vol. 24; no. 9; pp. 1225 - 1234
• Main Authors: Schafflick, David, Wolbert, Jolien, Heming, Michael, Thomas, Christian, Hartlehnert, Maike, Börsch, Anna-Lena, Ricci, Alessio, Martín-Salamanca, Sandra, Li, Xiaolin, Lu, I-Na, Pawlak, Mathias, Minnerup, Jens, Strecker, Jan-Kolja, Seidenbecher, Thomas, Meuth, Sven G., Hidalgo, Andres, Liesz, Arthur, Wiendl, Heinz, Meyer zu Horste, Gerd
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.09.2021; Nature Publishing Group
• Subjects: 14; 38/32; 38/39; 38/91; 631/61/514/1949; 692/698/1688/1366; 692/699/249/2510; 692/699/375/1666; Animal Genetics and Genomics; Animals; B cells; B-Lymphocytes - immunology; Behavioral Sciences; Biological Techniques; Biomedical and Life Sciences; Biomedicine; Bone marrow; Cerebrospinal fluid; Choroid plexus; Development and progression; Dura mater; Health aspects; Homeostasis; Immunology; Inflammation; Leukocytes; Lymphocytes; Lymphocytes B; Meninges; Meninges - immunology; Mice; Neurobiology; Neurosciences; Parenchyma; Physiological aspects; Precursor Cells, B-Lymphoid - immunology; Progenitor cells; Rats; Single-Cell Analysis; Skull; Stem cells; Tissues; Germany
• ISSN: 1097-6256; 1546-1726; 1546-1726
• DOI: 10.1038/s41593-021-00880-y

The CNS is ensheathed by the meninges and cerebrospinal fluid, and recent findings suggest that these CNS-associated border tissues have complex immunological functions. Unlike myeloid lineage cells, lymphocytes in border compartments have yet to be thoroughly characterized. Based on single-cell transcriptomics, we here identified a highly location-specific composition and expression profile of tissue-resident leukocytes in CNS parenchyma, pia-enriched subdural meninges, dura mater, choroid plexus and cerebrospinal fluid. The dura layer of the meninges contained a large population of B cells under homeostatic conditions in mice and rats. Murine dura B cells exhibited slow turnover and long-term tissue residency, and they matured in experimental neuroinflammation. 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. This identified the dura as an unexpected site of B cell residence and potentially of development in both homeostasis and neuroinflammation. The skull dura contains B cells and B lineage precursors under homeostatic conditions. These cells are long-term tissue resident and mature upon neuroinflammation. This identifies the dura as a site of B cell residence and potentially development.