Abnormal B-Cell Exosome Proapoptotic and Antiapoptotic Cargo in Multiple Sclerosis: Potential Implication in Progressive Disease Biology.

Authors

Gautier Breville, Ayman Rezk, Samuel Weissman, Diego A Espinoza, Simon Thebault, Luana D Yamashita, Yeseul Kim, Mihir Kakara, Liljana Nedelkoska, Nicole Doyon-Reale, Celine Delucinge-Vivier, Leah Zuroff, Hanane Touil, Paul Stemmer, Joyce A Benjamins, Robert P Lisak, Amit Bar-Or

Published in

Neurology(R) neuroimmunology & neuroinflammation. Volume 13. Issue 4. Pages e200590. Epub Jun 09, 2026.

Abstract

Compartmentalized CNS inflammation involving B cells is implicated in gray matter injury and disease progression in multiple sclerosis (MS). Products secreted by B cells of patients with MS can kill oligodendrocytes and neurons, a cytotoxicity conferred by their exosome-enriched extracellular vesicle (Ex En) fraction.
To explore the potential molecular mediators of this cytotoxicity, we profiled proteomic and transcriptomic cargo of Ex En isolated from B cells of patients with treatment-naive MS and matched healthy controls.
MS B-cell-derived Ex En appeared enriched in cell-death-associated proteins (including fibrinogen, complement C9, APP, and SPARC) and deficient in cell-survival-associated proteins (such as galectin-3). Abnormal enrichment for cell-death proteins was supported by gene set enrichment analysis. Protein pathway analysis revealed densely connected prodeath modules in the MS B-cell-derived Ex En, contrasting with homeostatic signatures in controls. Transcriptomic analysis further revealed that Ex En of MS B cells appeared to carry reduced levels of miRNAs (miR-182, miR-212, and miR-1270) known to inhibit apoptosis.
Our findings indicate that B-cell-derived Ex En of patients with MS, previously shown to impair neuronal and glial survival, harbor an abnormal cytotoxic molecular profile that may contribute to CNS-compartmentalized injury and progressive MS biology.

PMID:
42378709
Bibliographic data and abstract were imported from PubMed on 01 Jul 2026.

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