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

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

Pröbstel, Anne-Katrin; Zhou, Xiaoyuan; Baumann, Ryan; Wischnewski, Sven; Kutza, Michael; Rojas, Olga L; Sellrie, Katrin; Bischof, Antje; Kim, Kicheol; Ramesh, Akshaya; Dandekar, Ravi; Greenfield, Ariele L; Schubert, Ryan D; Bisanz, Jordan E; Vistnes, Stephanie; Khaleghi, Khashayar; Landefeld, James; Kirkish, Gina; Liesche-Starnecker, Friederike; Ramaglia, Valeria; Singh, Sneha; Tran, Edwina B; Barba, Patrick; Zorn, Kelsey; Oechtering, Johanna; Forsberg, Karin; Shiow, Lawrence R; Henry, Roland G;...     »

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.      «

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, resul...     »