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Gut microbiota-specific IgA+ B cells traffic to the CNS in active multiple sclerosis.
Journal article

Gut microbiota-specific IgA+ B cells traffic to the CNS in active multiple sclerosis.

  • Pröbstel AK Department of Neurology, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA. anne-katrin.proebstel@usb.ch sergio.baranzini@ucsf.edu.
  • Zhou X Department of Neurology, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Baumann R Department of Neurology, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Wischnewski S Department of Neurology and Mannheim Center for Translational Neurosciences, Medical Faculty Mannheim, University of Heidelberg, 68167 Mannheim, Germany.
  • Kutza M Department of Neurology and Mannheim Center for Translational Neurosciences, Medical Faculty Mannheim, University of Heidelberg, 68167 Mannheim, Germany.
  • Rojas OL Department of Immunology, University of Toronto, Toronto, ON M5S 18A, Canada.
  • Sellrie K Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, 14776 Potsdam, Germany.
  • Bischof A Department of Neurology, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Kim K Department of Neurology, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Ramesh A Department of Neurology, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Dandekar R Department of Neurology, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Greenfield AL Department of Neurology, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Schubert RD Department of Neurology, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Bisanz JE Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143, USA.
  • Vistnes S Eli and Edythe Broad Center for Stem Cell Research and Regeneration Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
  • Khaleghi K Department of Immunology, University of Toronto, Toronto, ON M5S 18A, Canada.
  • Landefeld J Department of Neurology, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Kirkish G Department of Neurology, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Liesche-Starnecker F Department of Neuropathology, School of Medicine, Institute of Pathology, Technical University Munich, 81675 Munich, Germany.
  • Ramaglia V Department of Neurology and Mannheim Center for Translational Neurosciences, Medical Faculty Mannheim, University of Heidelberg, 68167 Mannheim, Germany.
  • Singh S Department of Neurology, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Tran EB Department of Neurology, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Barba P Department of Neurology, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Zorn K Department of Neurology, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Oechtering J Neurologic Clinic and Policlinic and Research Center for Clinical Neuroimmunology and Neuroscience Basel, Departments of Medicine, Biomedicine, and Clinical Research, University Hospital of Basel, University of Basel, 4031 Basel, Switzerland.
  • Forsberg K Department of Clinical Science, Neurosciences, Umeå University, 90185 Umeå, Sweden.
  • Shiow LR Eli and Edythe Broad Center for Stem Cell Research and Regeneration Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
  • Henry RG Department of Neurology, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Graves J Department of Neurology, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Cree BAC Department of Neurology, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Hauser SL Department of Neurology, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Kuhle J Neurologic Clinic and Policlinic and Research Center for Clinical Neuroimmunology and Neuroscience Basel, Departments of Medicine, Biomedicine, and Clinical Research, University Hospital of Basel, University of Basel, 4031 Basel, Switzerland.
  • Gelfand JM Department of Neurology, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Andersen PM Department of Clinical Science, Neurosciences, Umeå University, 90185 Umeå, Sweden.
  • Schlegel J Department of Neuropathology, School of Medicine, Institute of Pathology, Technical University Munich, 81675 Munich, Germany.
  • Turnbaugh PJ Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143, USA.
  • Seeberger PH Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, 14776 Potsdam, Germany.
  • Gommerman JL Department of Immunology, University of Toronto, Toronto, ON M5S 18A, Canada.
  • Wilson MR Department of Neurology, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Schirmer L Department of Neurology and Mannheim Center for Translational Neurosciences, Medical Faculty Mannheim, University of Heidelberg, 68167 Mannheim, Germany.
  • Baranzini SE Department of Neurology, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA. anne-katrin.proebstel@usb.ch sergio.baranzini@ucsf.edu.
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  • 2020-11-21
Published in:
  • Science immunology. - 2020
English Changes in gut microbiota composition and a diverse role of B cells have recently been implicated in multiple sclerosis (MS), a central nervous system (CNS) autoimmune disease. Immunoglobulin A (IgA) is a key regulator at the mucosal interface. However, whether gut microbiota shape IgA responses and what role IgA+ cells have in neuroinflammation are unknown. Here, we identify IgA-bound taxa in MS and show that IgA-producing cells specific for MS-associated taxa traffic to the inflamed CNS, resulting in a strong, compartmentalized IgA enrichment in active MS and other neuroinflammatory diseases. Unlike previously characterized polyreactive anti-commensal IgA responses, CNS IgA cross-reacts with surface structures on specific bacterial strains but not with brain tissue. These findings establish gut microbiota-specific IgA+ cells as a systemic mediator in MS and suggest a critical role of mucosal B cells during active neuroinflammation with broad implications for IgA as an informative biomarker and IgA-producing cells as an immune subset to harness for therapeutic interventions.
Language
  • English
Open access status
closed
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Persistent URL
https://sonar.ch/global/documents/64110
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