B cells in the retinal pigment epithelium change with aging and IgM availability

Maintenance of the retina, the CNS tissue responsible for vision, is critical during aging. Historically considered immune privileged, the retina was thought to lack traditional immune components with resident glial cells maintaining tissue integrity. Emerging evidence suggests that immune suppression, rather than immune absence, governs retinal tolerance. Here, we identify B lymphocytes isolated from the retinal pigment epithelium (RPE), a CNS barrier niche, and show that their activation state and antibody repertoire are associated with secreted immunoglobulin M (IgM) availability and aging. In the absence of secreted IgM, B cells isolated from the RPE display a more activated phenotype and an altered B cell receptor repertoire, with age further modifying VH usage and CDR-H3 properties and expansion. Functionally, RPE B cells secrete antibodies following stimulation. These findings provide a foundation for understanding humoral regulation in CNS barrier tissues and mechanisms linking immune function to retinal aging and health.