T–B cell cooperation in ectopic lymphoid follicles propagates CNS autoimmunity

Kolz, Anna ; Rosa del Val, Clara de la ; Syma, Isabel J. ; McGrath, Sarah ; Kavaka, Vladyslav ; Schmitz, Rosa ; Thomann, Anna S. ; Kerschensteiner, Martin ; Beltran, Eduardo ; Kawakami, Naoto und Peters, Anneli (2025): T–B cell cooperation in ectopic lymphoid follicles propagates CNS autoimmunity. In: Science Immunology, Vol. 10, No. 106, eadn2784

Abstract

Meningeal ectopic lymphoid follicle (eLF)–like structures have been described in multiple sclerosis, but their role in central nervous system (CNS) autoimmunity is unclear. Here, we used a T helper 17 (TH17) adoptive transfer experimental autoimmune encephalomyelitis model featuring formation of eLFs. Single-cell RNA sequencing revealed that clusters of activated B cells and B1/marginal zone–like B cells were overrepresented in the CNS and identified B cells poised for undergoing germinal center reactions and clonal expansion in the CNS. Using intravital imaging to directly visualize TH17–B cell interactions, we demonstrated that T and B cells form long-lasting antigen-specific contacts in meningeal eLFs that result in reactivation of autoreactive T cells. CNS T cells depended on CNS B cells to maintain a proinflammatory cytokine profile. Our study reveals that extensive T–B cell cooperation occurs in meningeal eLFs, promoting both B cell differentiation and T cell reactivation, and may thereby propagate smoldering inflammation in the CNS.

• Item Type: Journal article
• Faculties: Medicine > Biomedical Center; Medicine > Munich Cluster for Systems Neurology (SyNergy); Medicine > Medical Center of the University of Munich > Neurological Clinic and Polyclinic with Friedrich Baur Institute
• Research Centers: Munich Center for Neurosciences – Brain & Mind
• Subjects: 600 Technology > 610 Medicine and health
• ISSN: 2470-9468
• Language: English
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 390857198