Selective emergence of antibody-secreting cells in the multiple sclerosis brain
Laurens Bogers, Hendrik J. Engelenburg, Malou Janssen, Peter‐Paul A. Unger, Marie‐José Melief, Annet F. Wierenga‐Wolf, Cheng‐Chih Hsiao, Matthew R. J. Mason, Jörg Hamann, Jamie van Langelaar, Joost Smolders, Marvin M. van Luijn
Abstract
BACKGROUND: Although distinct brain-homing B cells have been identified in multiple sclerosis (MS), it is unknown how these further evolve to contribute to local pathology. We explored B-cell maturation in the central nervous system (CNS) of MS patients and determined their association with immunoglobulin (Ig) production, T-cell presence, and lesion formation. METHODS: Ex vivo flow cytometry was performed on post-mortem blood, cerebrospinal fluid (CSF), meninges and white matter from 28 MS and 10 control brain donors to characterize B cells and antibody-secreting cells (ASCs). MS brain tissue sections were analysed with immunostainings and microarrays. IgG index and CSF oligoclonal bands were measured with nephelometry, isoelectric focusing, and immunoblotting. Blood-derived B cells were cocultured under T follicular helper-like conditions to evaluate their ASC-differentiating capacity in vitro. FINDINGS: memory T cells positively correlated with ASC presence, reflected by local interplay with T cells. INTERPRETATION: memory T cells. FUNDING: Stichting MS Research (19-1057 MS; 20-490f MS), National MS Fonds (OZ2018-003).