Gut microbiota–specific iga+ B cells traffic to the CNS in active multiple sclerosis

Anne Katrin Pröbstel, Xiaoyuan Zhou, Ryan Baumann, Sven Wischnewski, Michael Kutza, Olga L. Rojas, Katrin Sellrie, Antje Bischof, Kicheol Kim, Akshaya Ramesh, Ravi Dandekar, Ariele L. Greenfield, Ryan D. Schubert, Jordan E. Bisanz, Stephanie Vistnes, Khashayar Khaleghi, James Landefeld, Gina Kirkish, Friederike Liesche-Starnecker, Valeria RamagliaSneha Singh, Edwina B. Tran, Patrick Barba, Kelsey Zorn, Johanna Oechtering, Karin Forsberg, Lawrence R. Shiow, Roland G. Henry, Jennifer Graves, Bruce A.C. Cree, Stephen L. Hauser, Jens Kuhle, Jeffrey M. Gelfand, Peter M. Andersen, Jürgen Schlegel, Peter J. Turnbaugh, Peter H. Seeberger, Jennifer L. Gommerman, Michael R. Wilson, Lucas Schirmer, Sergio E. Baranzini

    Research output: Contribution to journalArticlepeer-review

    29 Scopus citations

    Abstract

    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.

    Original languageEnglish (US)
    Article numberabc7191
    JournalScience Immunology
    Volume5
    Issue number53
    DOIs
    StatePublished - Nov 20 2020

    All Science Journal Classification (ASJC) codes

    • Immunology and Allergy
    • Immunology

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