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The presence of meningeal B cell aggregates has been correlated with worse disease. However, the functional role of these meningeal B cell aggregates is not understood. Here, we use a mouse model of multiple sclerosis, the spontaneous opticospinal encephalomyelitis model, which is built on the double transgenic expression of myelin oligodendrocyte glycoprotein-specific T-cell and B-cell receptors, to show that the formation of meningeal B cell aggregates is dependent on the expression of \u03b14 integrins by antigen-specific T cells. T cell-conditional genetic ablation of \u03b14 integrins in opticospinal encephalomyelitis mice impaired the formation of meningeal B cell aggregates, and surprisingly, led to a higher disease incidence as compared to opticospinal encephalomyelitis mice with \u03b14 integrin-sufficient T cells. B cell-conditional ablation of \u03b14 integrins in opticospinal encephalomyelitis mice resulted in the entire abrogation of the formation of meningeal B cell aggregates, and opticospinal encephalomyelitis mice with \u03b14 integrin-deficient B cells suffered from a higher disease burden than regular opticospinal encephalomyelitis mice. While anti-CD20 antibody-mediated systemic depletion of B cells in opticospinal encephalomyelitis mice after onset of disease failed to efficiently decrease meningeal B cell aggregates without significantly modulating disease progression, treatment with anti-CD19 chimeric antigen receptor-T cells eliminated meningeal B cell aggregates and exacerbated clinical disease in opticospinal encephalomyelitis mice. Since about 20% of B cells in organized meningeal B cell aggregates produced either IL-10 or IL-35, we propose that meningeal B cell aggregates might also have an immunoregulatory function as to the immunopathology in adjacent spinal cord white matter. The immunoregulatory function of meningeal B cell aggregates needs to be considered when designing highly efficient therapies directed against meningeal B cell aggregates for clinical application in multiple sclerosis.<\/jats:p>","DOI":"10.1093\/brain\/awab093","type":"journal-article","created":{"date-parts":[[2021,3,6]],"date-time":"2021-03-06T20:09:49Z","timestamp":1615061389000},"page":"1697-1710","source":"Crossref","is-referenced-by-count":48,"title":["Formation and immunomodulatory function of meningeal B cell aggregates\u00a0in progressive CNS autoimmunity"],"prefix":"10.1093","volume":"144","author":[{"given":"Meike","family":"Mitsdoerffer","sequence":"first","affiliation":[{"name":"Klinikum rechts der Isar, Department of Neurology, Technical University of Munich, 81675 Munich, Germany"},{"name":"Klinikum rechts der Isar, Institute for Experimental Neuroimmunology, Technical University of Munich, 81675 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Di Liberto","sequence":"additional","affiliation":[{"name":"Division of Clinical Pathology, Department of Pathology and Immunology, Geneva Faculty of Medicine, Centre M\u00e9dical Universitaire, 1211 Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"D\u00f6tsch","sequence":"additional","affiliation":[{"name":"Institute for Medical Microbiology, Immunology, and Hygiene, Technical University of Munich, 81675 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8066-7539","authenticated-orcid":false,"given":"Christopher","family":"Sie","sequence":"additional","affiliation":[{"name":"Klinikum rechts der Isar, Institute for Experimental Neuroimmunology, Technical University of Munich, 81675 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingrid","family":"Wagner","sequence":"additional","affiliation":[{"name":"Division of Clinical Pathology, Department of Pathology and Immunology, Geneva Faculty of Medicine, Centre M\u00e9dical Universitaire, 1211 Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monika","family":"Pfaller","sequence":"additional","affiliation":[{"name":"Klinikum rechts der Isar, Institute for Experimental Neuroimmunology, Technical University of Munich, 81675 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Kreutzfeldt","sequence":"additional","affiliation":[{"name":"Division of Clinical Pathology, Department of Pathology and Immunology, Geneva Faculty of Medicine, Centre M\u00e9dical Universitaire, 1211 Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Fr\u00e4\u00dfle","sequence":"additional","affiliation":[{"name":"Institute for Medical Microbiology, Immunology, and Hygiene, Technical University of Munich, 81675 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lilian","family":"Aly","sequence":"additional","affiliation":[{"name":"Klinikum rechts der Isar, Department of Neurology, Technical University of Munich, 81675 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Knier","sequence":"additional","affiliation":[{"name":"Klinikum rechts der Isar, Department of Neurology, Technical University of Munich, 81675 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk H","family":"Busch","sequence":"additional","affiliation":[{"name":"Institute for Medical Microbiology, Immunology, and Hygiene, Technical University of Munich, 81675 Munich, Germany"},{"name":"National Center for Infection Research (DZIF), Technical University of Munich, 81675 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doron","family":"Merkler","sequence":"additional","affiliation":[{"name":"Division of Clinical Pathology, Department of Pathology and Immunology, Geneva Faculty of Medicine, Centre M\u00e9dical Universitaire, 1211 Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3633-0955","authenticated-orcid":false,"given":"Thomas","family":"Korn","sequence":"additional","affiliation":[{"name":"Klinikum rechts der Isar, Department of Neurology, Technical University of Munich, 81675 Munich, Germany"},{"name":"Klinikum rechts der Isar, Institute for Experimental Neuroimmunology, Technical University of Munich, 81675 Munich, Germany"},{"name":"Munich Cluster for Systems Neurology (SyNergy), DZNE site Munich, 81377 Munich, 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