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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.

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Institute of Neuropathology, University Medical Center, 37099 Göttingen, Germany.
Department of Neurology, Klinikum rechts der Isar, Technische Universität München, 81675 Munich, Germany.
Monash Regenerative Medicine Institute, Monash University, 3800 Melbourne, Australia.
Multiple Sclerosis Research Group, Monash University, 3800 Melbourne, Australia.
Department of Neurology, University of California, San Francisco, CA 94158.
Program in Immunology, University of California, San Francisco, CA 94158.
Munich Cluster for Systems Neurology (SyNergy), 81675 Munich, Germany.
Institute of Neuropathology, University Medical Center, 37099 Göttingen, Germany;
Department of Neurology, University Medical Center, 37099 Göttingen, Germany.


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.


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

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