T-bet+ CXCR3+ B cells drive hyperreactive B-T cell interactions in multiple sclerosis.

IF 11.7 1区医学 Q1 CELL BIOLOGY

Cell Reports Medicine Pub Date : 2025-03-18 DOI:10.1016/j.xcrm.2025.102027

Ivan Jelcic, Reza Naghavian, Imran Fanaswala, Will Macnair, Cinzia Esposito, Daniela Calini, Yanan Han, Zoe Marti, Catarina Raposo, Jacobo Sarabia Del Castillo, Pietro Oldrati, Daniel Erny, Veronika Kana, Galina Zheleznyakova, Faiez Al Nimer, Björn Tackenberg, Ina Reichen, Mohsen Khademi, Fredrik Piehl, Mark D Robinson, Ilijas Jelcic, Mireia Sospedra, Lucas Pelkmans, Dheeraj Malhotra, Richard Reynolds, Maja Jagodic, Roland Martin

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引用次数: 0

Abstract

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS). Self-peptide-dependent autoproliferation (AP) of B and T cells is a key mechanism in MS. Here, we show that pro-inflammatory B-T cell-enriched cell clusters (BTECs) form during AP and mirror features of a germinal center reaction. T-bet+CXCR3+ B cells are the main cell subset amplifying and sustaining their counterpart Th1 cells via interferon (IFN)-γ and are present in highly inflamed meningeal tissue. The underlying B cell activation signature is reflected by epigenetic modifications and receptor-ligand interactions with self-reactive T cells. AP+ CXCR3+ B cells show marked clonal evolution from memory to somatically hypermutated plasmablasts and upregulation of IFN-γ-related genes. Our data underscore a key role of T-bet+CXCR3+ B cells in the pathogenesis of MS in both the peripheral immune system and the CNS compartment, and thus they appear to be involved in both early relapsing-remitting disease and the chronic stage.

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来源期刊

Cell Reports Medicine Biochemistry, Genetics and Molecular Biology-Biochemistry, Genetics and Molecular Biology (all)

CiteScore

15.00

自引率

1.40%

发文量

231

审稿时长

40 days

期刊介绍： Cell Reports Medicine is an esteemed open-access journal by Cell Press that publishes groundbreaking research in translational and clinical biomedical sciences, influencing human health and medicine. Our journal ensures wide visibility and accessibility, reaching scientists and clinicians across various medical disciplines. We publish original research that spans from intriguing human biology concepts to all aspects of clinical work. We encourage submissions that introduce innovative ideas, forging new paths in clinical research and practice. We also welcome studies that provide vital information, enhancing our understanding of current standards of care in diagnosis, treatment, and prognosis. This encompasses translational studies, clinical trials (including long-term follow-ups), genomics, biomarker discovery, and technological advancements that contribute to diagnostics, treatment, and healthcare. Additionally, studies based on vertebrate model organisms are within the scope of the journal, as long as they directly relate to human health and disease.