AUTHOR=Haas Jürgen , Rudolph Henriette , Costa Leonardo , Faller Simon , Libicher Saskia , Würthwein Cornelia , Jarius Sven , Ishikawa Hiroshi , Stump-Guthier Carolin , Tenenbaum Tobias , Schwerk Christian , Schroten Horst , Wildemann Brigitte TITLE=The Choroid Plexus Is Permissive for a Preactivated Antigen-Experienced Memory B-Cell Subset in Multiple Sclerosis JOURNAL=Frontiers in Immunology VOLUME=11 YEAR=2021 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2020.618544 DOI=10.3389/fimmu.2020.618544 ISSN=1664-3224 ABSTRACT=
The role of B cells in multiple sclerosis (MS) is increasingly recognized. B cells undergo compartmentalized redistribution in blood and cerebrospinal fluid (CSF) during active MS, whereby memory B cells accumulate in the CSF. While B-cell trafficking across the blood–brain barrier has been intensely investigated, cellular diapedesis through the blood–CSF barrier (BCSFB) is incompletely understood. To investigate how B cells interact with the choroid plexus to transmigrate into the CSF we isolated circulating B cells from healthy donors (HC) and MS patients, utilized an inverted cell culture filter system of human choroid plexus papilloma (HIBCPP) cells to determine transmigration rates of B-cell subsets, immunofluorescence, and electron microscopy to analyze migration routes, and qRT-PCR to determine cytokines/chemokines mediating B-cell diapedesis. We also screened the transcriptome of intrathecal B cells from MS patients. We found, that spontaneous transmigration of HC- and MS-derived B cells was scant, yet increased significantly in response to B-cell specific chemokines CXCL-12/CXCL-13, was further boosted upon pre-activation and occurred