| Title: |
Formation and immunomodulatory function of meningeal B cell aggregates in progressive CNS autoimmunity |
| Authors: |
Mitsdoerffer, Meike; Di Liberto, Giovanni; Dötsch, Sarah; Sie, Christopher; Wagner, Ingrid; Pfaller, Monika; Kreutzfeldt, Mario; Fräßle, Simon; Aly, Lilian; Knier, Benjamin; Busch, Dirk H.; Merkler, Doron; Korn, Thomas |
| Contributors: |
Mitsdoerffer, Meike; Di Liberto, Giovanni; Dötsch, Sarah; Sie, Christopher; Wagner, Ingrid; Pfaller, Monika; Kreutzfeldt, Mario; Fräßle, Simon; Aly, Lilian; Knier, Benjamin; Busch, Dirk H.; Merkler, Doron; Korn, Thomas |
| Publication Year: |
2021 |
| Collection: |
Georg-August-Universität Göttingen: GoeScholar |
| Description: |
Meningeal B lymphocyte aggregates have been described in autopsy material of patients with chronic multiple sclerosis. The presence of meningeal B cell aggregates has been correlated with worse disease. However, the functional role of these meningeal B cell aggregates is not understood. Here, we use a mouse model of multiple sclerosis, the spontaneous opticospinal encephalomyelitis model, which is built on the double transgenic expression of myelin oligodendrocyte glycoprotein-specific T-cell and B-cell receptors, to show that the formation of meningeal B cell aggregates is dependent on the expression of α4 integrins by antigen-specific T cells. T cell-conditional genetic ablation of α4 integrins in opticospinal encephalomyelitis mice impaired the formation of meningeal B cell aggregates, and surprisingly, led to a higher disease incidence as compared to opticospinal encephalomyelitis mice with α4 integrin-sufficient T cells. B cell-conditional ablation of α4 integrins in opticospinal encephalomyelitis mice resulted in the entire abrogation of the formation of meningeal B cell aggregates, and opticospinal encephalomyelitis mice with α4 integrin-deficient B cells suffered from a higher disease burden than regular opticospinal encephalomyelitis mice. While anti-CD20 antibody-mediated systemic depletion of B cells in opticospinal encephalomyelitis mice after onset of disease failed to efficiently decrease meningeal B cell aggregates without significantly modulating disease progression, treatment with anti-CD19 chimeric antigen receptor-T cells eliminated meningeal B cell aggregates and exacerbated clinical disease in opticospinal encephalomyelitis mice. Since about 20% of B cells in organized meningeal B cell aggregates produced either IL-10 or IL-35, we propose that meningeal B cell aggregates might also have an immunoregulatory function as to the immunopathology in adjacent spinal cord white matter. The immunoregulatory function of meningeal B cell aggregates needs to be considered when designing highly efficient ... |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
TRR 274: Checkpoints of Central Nervous System Recovery; TRR 274 %7C A01: Blimp1 as a checkpoint for distinct functions of CNS Treg cells; https://rdp.sfb274.de/literature/publications/17 |
| DOI: |
10.1093/brain/awab093 |
| Availability: |
https://resolver.sub.uni-goettingen.de/purl?gro-2/113008; https://doi.org/10.1093/brain/awab093; https://rdp.sfb274.de/literature/publications/17 |
| Rights: |
info:eu-repo/semantics/openAccess |
| Accession Number: |
edsbas.75DCD8E9 |
| Database: |
BASE |