Pathogenic T-bet+ memory B cells worsen multiple sclerosis through myeloid cell activation

Authors

Jain, R. W., Goiko, M., Mendes, A., Xue, S., Zein, S., Gorter, R. P., Morch, M. T., Prat, A., Li, R., Yong, V. W.

Abstract

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-{gamma} 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-{gamma}-facilitated interactions with microglia/macrophages.

Preprint server: bioRxiv
The authors list and abstract were imported from bioRxiv on 07 Sep 2026.

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