Anti-CD20 Depletes Meningeal B Cells but Does Not Halt the Formation of Meningeal Ectopic Lymphoid Tissue.


Journal

Neurology(R) neuroimmunology & neuroinflammation
ISSN: 2332-7812
Titre abrégé: Neurol Neuroimmunol Neuroinflamm
Pays: United States
ID NLM: 101636388

Informations de publication

Date de publication:
02 07 2021
Historique:
received: 25 01 2021
accepted: 08 03 2021
entrez: 22 5 2021
pubmed: 23 5 2021
medline: 22 1 2022
Statut: epublish

Résumé

To investigate whether anti-CD20 B-cell-depleting monoclonal antibodies (ɑCD20 mAbs) inhibit the formation or retention of meningeal ectopic lymphoid tissue (mELT) in a murine model of multiple sclerosis (MS). We used a spontaneous chronic experimental autoimmune encephalomyelitis (EAE) model of mice with mutant T-cell and B-cell receptors specific for myelin oligodendrocyte glycoprotein (MOG), which develop meningeal inflammatory infiltrates resembling those described in MS. ɑCD20 mAbs were administered in either a preventive or a treatment regimen. The extent and cellular composition of mELT was assessed by histology and immunohistochemistry. ɑCD20 mAb, applied in a paradigm to either prevent or treat EAE, did not alter the disease course in either condition. However, ɑCD20 mAb depleted virtually all B cells from the meningeal compartment but failed to prevent the formation of mELT altogether. Because of the absence of B cells, mELT was less densely populated with immune cells and the cellular composition was changed, with increased neutrophil granulocytes. These results demonstrate that, in CNS autoimmune disease, meningeal inflammatory infiltrates may form and persist in the absence of B cells. Together with the finding that ɑCD20 mAb does not ameliorate spontaneous chronic EAE with mELT, our data suggest that mELT may have yet unknown capacities that are independent of B cells and contribute to CNS autoimmunity.

Identifiants

pubmed: 34021057
pii: 8/4/e1012
doi: 10.1212/NXI.0000000000001012
pmc: PMC8143698
pii:
doi:

Substances chimiques

Antibodies, Monoclonal 0
Antigens, CD20 0
Immunologic Factors 0
Myelin-Oligodendrocyte Glycoprotein 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Commentaires et corrections

Type : CommentIn

Informations de copyright

Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

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Auteurs

Rosa Margareta Brand (RM)

From the Department of Neurology (R.M.B., V.F., J.D., M.P., F.R.F., K.L.-H.), School of Medicine, Technical University of Munich; Department of Neuropathology (H.R.), Charité - Universitätsmedizin Berlin; Department of Neurology (B.H.), School of Medicine, Technical University of Munich, Munich Cluster of Systems Neurology (SyNergy), Germany; and Comparative Experimental Pathology (CEP) (K.S.), Department of Pathology, School of Medicine, Technical University of Munich, Germany.

Verena Friedrich (V)

From the Department of Neurology (R.M.B., V.F., J.D., M.P., F.R.F., K.L.-H.), School of Medicine, Technical University of Munich; Department of Neuropathology (H.R.), Charité - Universitätsmedizin Berlin; Department of Neurology (B.H.), School of Medicine, Technical University of Munich, Munich Cluster of Systems Neurology (SyNergy), Germany; and Comparative Experimental Pathology (CEP) (K.S.), Department of Pathology, School of Medicine, Technical University of Munich, Germany.

Jolien Diddens (J)

From the Department of Neurology (R.M.B., V.F., J.D., M.P., F.R.F., K.L.-H.), School of Medicine, Technical University of Munich; Department of Neuropathology (H.R.), Charité - Universitätsmedizin Berlin; Department of Neurology (B.H.), School of Medicine, Technical University of Munich, Munich Cluster of Systems Neurology (SyNergy), Germany; and Comparative Experimental Pathology (CEP) (K.S.), Department of Pathology, School of Medicine, Technical University of Munich, Germany.

Monika Pfaller (M)

From the Department of Neurology (R.M.B., V.F., J.D., M.P., F.R.F., K.L.-H.), School of Medicine, Technical University of Munich; Department of Neuropathology (H.R.), Charité - Universitätsmedizin Berlin; Department of Neurology (B.H.), School of Medicine, Technical University of Munich, Munich Cluster of Systems Neurology (SyNergy), Germany; and Comparative Experimental Pathology (CEP) (K.S.), Department of Pathology, School of Medicine, Technical University of Munich, Germany.

Francesca Romana de Franchis (F)

From the Department of Neurology (R.M.B., V.F., J.D., M.P., F.R.F., K.L.-H.), School of Medicine, Technical University of Munich; Department of Neuropathology (H.R.), Charité - Universitätsmedizin Berlin; Department of Neurology (B.H.), School of Medicine, Technical University of Munich, Munich Cluster of Systems Neurology (SyNergy), Germany; and Comparative Experimental Pathology (CEP) (K.S.), Department of Pathology, School of Medicine, Technical University of Munich, Germany.

Helena Radbruch (H)

From the Department of Neurology (R.M.B., V.F., J.D., M.P., F.R.F., K.L.-H.), School of Medicine, Technical University of Munich; Department of Neuropathology (H.R.), Charité - Universitätsmedizin Berlin; Department of Neurology (B.H.), School of Medicine, Technical University of Munich, Munich Cluster of Systems Neurology (SyNergy), Germany; and Comparative Experimental Pathology (CEP) (K.S.), Department of Pathology, School of Medicine, Technical University of Munich, Germany.

Bernhard Hemmer (B)

From the Department of Neurology (R.M.B., V.F., J.D., M.P., F.R.F., K.L.-H.), School of Medicine, Technical University of Munich; Department of Neuropathology (H.R.), Charité - Universitätsmedizin Berlin; Department of Neurology (B.H.), School of Medicine, Technical University of Munich, Munich Cluster of Systems Neurology (SyNergy), Germany; and Comparative Experimental Pathology (CEP) (K.S.), Department of Pathology, School of Medicine, Technical University of Munich, Germany.

Katja Steiger (K)

From the Department of Neurology (R.M.B., V.F., J.D., M.P., F.R.F., K.L.-H.), School of Medicine, Technical University of Munich; Department of Neuropathology (H.R.), Charité - Universitätsmedizin Berlin; Department of Neurology (B.H.), School of Medicine, Technical University of Munich, Munich Cluster of Systems Neurology (SyNergy), Germany; and Comparative Experimental Pathology (CEP) (K.S.), Department of Pathology, School of Medicine, Technical University of Munich, Germany.

Klaus Lehmann-Horn (K)

From the Department of Neurology (R.M.B., V.F., J.D., M.P., F.R.F., K.L.-H.), School of Medicine, Technical University of Munich; Department of Neuropathology (H.R.), Charité - Universitätsmedizin Berlin; Department of Neurology (B.H.), School of Medicine, Technical University of Munich, Munich Cluster of Systems Neurology (SyNergy), Germany; and Comparative Experimental Pathology (CEP) (K.S.), Department of Pathology, School of Medicine, Technical University of Munich, Germany. klaus.lehmann-horn@tum.de.

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