Pathogenic T-bet+ memory B cells worsen multiple sclerosis through myeloid cell activation
- 1University of Calgary
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.
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BibTeX
@misc{jain2026pathogenic,
title = {{Pathogenic T-bet+ memory B cells worsen multiple sclerosis through myeloid cell activation}},
author = {R. W. Jain and M. Goiko and A. Mendes and S. Xue and S. Zein and R. P. Gorter and M. T. Morch and A. Prat and R. Li and V. W. Yong},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.01.748682},
url = {https://www.biorxiv.org/content/10.64898/2026.09.01.748682v1},
note = {CC BY-NC},
}
RIS
TY - UNPB
TI - Pathogenic T-bet+ memory B cells worsen multiple sclerosis through myeloid cell activation
AU - R. W. Jain
AU - M. Goiko
AU - A. Mendes
AU - S. Xue
AU - S. Zein
AU - R. P. Gorter
AU - M. T. Morch
AU - A. Prat
AU - R. Li
AU - V. W. Yong
PY - 2026
DA - 2026/09/01
PB - bioRxiv
DO - 10.64898/2026.09.01.748682
UR - https://www.biorxiv.org/content/10.64898/2026.09.01.748682v1
AB - 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.
ER -