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Proc Natl Acad Sci U S A. 2018 Sep 25;115(39):9773-9778. doi: 10.1073/pnas.1810470115. Epub 2018 Sep 7.

Functional characterization of reappearing B cells after anti-CD20 treatment of CNS autoimmune disease.

Author information

1
Institute of Neuropathology, University Medical Center, 37099 Göttingen, Germany.
2
Department of Neurology, Klinikum rechts der Isar, Technische Universität München, 81675 Munich, Germany.
3
Monash Regenerative Medicine Institute, Monash University, 3800 Melbourne, Australia.
4
Multiple Sclerosis Research Group, Monash University, 3800 Melbourne, Australia.
5
Department of Neurology, University of California, San Francisco, CA 94158.
6
Program in Immunology, University of California, San Francisco, CA 94158.
7
Munich Cluster for Systems Neurology (SyNergy), 81675 Munich, Germany.
8
Institute of Neuropathology, University Medical Center, 37099 Göttingen, Germany; martin.weber@med.uni-goettingen.de.
9
Department of Neurology, University Medical Center, 37099 Göttingen, Germany.

Abstract

The anti-CD20 antibody ocrelizumab, approved for treatment of multiple sclerosis, leads to rapid elimination of B cells from the blood. The extent of B cell depletion and kinetics of their recovery in different immune compartments is largely unknown. Here, we studied how anti-CD20 treatment influences B cells in bone marrow, blood, lymph nodes, and spleen in models of experimental autoimmune encephalomyelitis (EAE). Anti-CD20 reduced mature B cells in all compartments examined, although a subpopulation of antigen-experienced B cells persisted in splenic follicles. Upon treatment cessation, CD20+ B cells simultaneously repopulated in bone marrow and spleen before their reappearance in blood. In EAE induced by native myelin oligodendrocyte glycoprotein (MOG), a model in which B cells are activated, B cell recovery was characterized by expansion of mature, differentiated cells containing a high frequency of myelin-reactive B cells with restricted B cell receptor gene diversity. Those B cells served as efficient antigen-presenting cells (APCs) for activation of myelin-specific T cells. In MOG peptide-induced EAE, a purely T cell-mediated model that does not require B cells, in contrast, reconstituting B cells exhibited a naive phenotype without efficient APC capacity. Our results demonstrate that distinct subpopulations of B cells differ in their sensitivity to anti-CD20 treatment and suggest that differentiated B cells persisting in secondary lymphoid organs contribute to the recovering B cell pool.

KEYWORDS:

B cell recovery; anti-CD20; experimental autoimmune encephalomyelitis; multiple sclerosis; secondary lymphoid organ

PMID:
30194232
PMCID:
PMC6166805
DOI:
10.1073/pnas.1810470115
[Indexed for MEDLINE]
Free PMC Article

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