Open AccessBcl6 controls meningeal Th17–B cell interaction in murine neuroinflammation
Author(s) -
Maike Hartlehnert,
AnnaLena Börsch,
Xin Li,
Miriam Burmeister,
Hanna Gerwien,
David Schafflick,
Michael Heming,
I-Na Lu,
Venu Narayanan,
JanKolja Strecker,
Anna Kolz,
Anneli Peters,
Gregory F. Wu,
Heinz Wiendl,
Lydia Sorokin,
Gerd Meyer zu Hörste
Publication year - 2021
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2023174118
Subject(s) - neuroinflammation , meninges , biology , bcl6 , b cell , microbiology and biotechnology , cxcl13 , immunology , follicular dendritic cells , inflammation , antibody , t cell , immune system , germinal center , antigen presenting cell , chemokine , neuroscience , chemokine receptor
Significance The meninges protect the central nervous system but also host lymphocytes in neuroinflammation. In human multiple sclerosis, preferentially B cells accumulate in the meninges. By generating a compartment-specific transcriptional map of meningeal versus parenchymal leukocytes in experimental neuroinflammation, we found a follicular phenotype of meningeal B cells and a corresponding follicular helper-like phenotype in meningeal Th17 cells. The meninges thus instructed a site-specific local phenotype to proinflammatory autoreactive T cells. We identified the transcription factor Bcl6 in Th17 cells to promote interactions with meningeal B cells, isotype-switching, and B cell-supporting chemokines. This may describe a mechanism controlling meningeal autoimmunity and helps understanding how the meninges, as a recently recognized immunologically active site, contribute to autoimmune tissue damage in multiple sclerosis.