A pathogenic and clonally expanded B cell transcriptome in active multiple sclerosis
Abstract
B cells serve as a key weapon against infectious diseases. They also contribute to multiple autoimmune diseases, including multiple sclerosis (MS) where depletion of B cells is a highly effective therapy. We describe a comprehensive profile of central nervous system (CNS)-specific transcriptional B cell phenotypes in MS at single-cell resolution with paired immune repertoires. We reveal a polyclonal immunoglobulin M (IgM) and IgG1 cerebrospinal fluid B cell expansion polarized toward an inflammatory, memory and plasmablast/plasma cell phenotype, with differential up-regulation of specific proinflammatory pathways. We did not find evidence that CNS B cells harbor a neurotropic virus. These data support the targeting of activated resident B cells in the CNS as a potentially effective strategy for control of treatment-resistant chronic disease.
- Publication:
-
Proceedings of the National Academy of Science
- Pub Date:
- September 2020
- DOI:
- 10.1073/pnas.2008523117
- Bibcode:
- 2020PNAS..11722932R