Heterogeneity of meningeal B cells reveals a lymphopoietic niche at the CNS borders [scRNA-seq]

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 35 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 calvaria- 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 40 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. scRNA-seq was performed on bulk preparations from mouse peripheral blood, tibial bone marrow, and dura mater from young and aged mice. Sequencing was completed in two batches: The first batch contained 3 mice from each age:tissue combination. The second batch contained peripheral blood and dura from 3 young and 4 old mice.