CNS-resident B cells develop locally into a pro-inflammatory age-associated phenotype during aging and after stroke

Aging and age-related diseases like ischemic stroke induce chronic lymphocyte recruitment into the CNS. Conflicting effects on post-stroke functional recovery, however, are secondary to the differences in responding lymphocyte populations that shift immunophenotype with injury and age. To better define CNS-localized B cell subsets, we used flow cytometry, single-cell RNA sequencing, and B cell receptor sequencing on B cells isolated from uninjured and post-stroke brains of aged male and female mice. We identified a novel B1b cell progenitor pool distinct from canonical pleural/peritoneal niches. Trajectory analysis showed progenitor transition into age-associated B cell (ABC) subsets, and clonal expansion of IgM ⁺ ABCs (ABC/B1b) and plasma cells following ischemic stroke. We also confirmed analogous ABCs and developing B cell populations in post-mortem human parenchymal tissue isolated from aged brain donors. These studies reveal unique B cell populations that can proliferate within the aging CNS and exhibit a conserved inflammatory signature across species.