Pathogenic T-bet + memory B cells worsen multiple sclerosis through myeloid cell activation
Year: 2026
Type: preprint
Abstract: Summary Depletion of B cells in multiple sclerosis (MS) is beneficial yet there is no defined pathogenic B cell subset in MS. Here, we demonstrate that T-bet + memory B cells are rare in control human brain specimens but are found in MS lesions. Transfer of murine T-bet + memory B cells into mice with ongoing experimental autoimmune encephalomyelitis (EAE), a model of MS, worsened their disability and demyelination. Microglia/macrophage density increased in central nervous system parenchyma even though B cells mostly remained in barriers. In culture, secreted factors from T-bet + memory B cells promoted macrophage migration. IFN-γ produced by T-bet + memory B cells activated microglia to secrete chemokines that further enabled macrophage migration. Consistent with their age-associated elevation, conditional deletion of T-bet in B cells lowered EAE severity in aged but not young mice. We define T-bet + memory B cells as pathogenic in EAE and MS through their IFN-γ-facilitated interactions with microglia/macrophages.
Language: English
Subfield: Clinical Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7210272316