Heterogeneity of meningeal B cells reveals a lymphopoietic niche at the CNS borders.

Brioschi, Simone; Wang, Wei-Le; Peng, Vincent; Wang, Meng; Shchukina, Irina; Greenberg, Zev J; Bando, Jennifer K; Jaeger, Natalia; Czepielewski, Rafael S; Swain, Amanda; Mogilenko, Denis A; Beatty, Wandy L; Bayguinov, Peter; Fitzpatrick, James A J; Schuettpelz, Laura G; Fronick, Catrina C; Smirnov, Igor; Kipnis, Jonathan; Shapiro, Virginia S; Wu, Gregory F; Gilfillan, Susan; Cella, Marina; Artyomov, Maxim N; Kleinstein, Steven H; Colonna, Marco

The meninges contain adaptive immune cells that provide immunosurveillance of the CNS. These cells are thought to derive from the systemic circulation. Through single-cell analyses, confocal imaging, bone marrow chimeras, and parabiosis experiments, we show that meningeal B cells derive locally from the calvaria, which harbors a bone marrow niche for hematopoiesis. B cells reach the meninges from the calvaria through specialized vascular connections. This calvarial-meningeal path of B cell development may provide the CNS with a constant supply of B cells educated by CNS antigens. Conversely, we show that a subset of antigen-experienced B cells that populate the meninges in aging mice are blood-borne. These results identify a private source for meningeal B cells. which may help maintain immune privilege within the CNS.