Weber, Martin S.

[["dc.bibliographiccitation.artnumber","201"],["dc.bibliographiccitation.journal","Frontiers in Immunology"],["dc.bibliographiccitation.volume","10"],["dc.contributor.author","Häusser-Kinzel, Silke"],["dc.contributor.author","Weber, Martin S."],["dc.date.accessioned","2019-07-09T11:50:12Z"],["dc.date.available","2019-07-09T11:50:12Z"],["dc.date.issued","2019"],["dc.description.abstract","Our pathophysiological concept of the most common central nervous system demyelinating disease, multiple sclerosis, strikingly evolved by recent discoveries suggesting that B lymphocytes substantially contribute in its initiation and chronic propagation. In this regard, activated B cells are nowadays considered to act as important antigen-presenting cells for the activation of T cells and as essential source of pro-inflammatory cytokines. Hereby, they create a milieu in which other immune cells differentiate and join an orchestrated inflammatory infiltration of the CNS. Without a doubt, this scientific leap was critically pioneered by the empirical use of anti-CD20 antibodies in recent clinical MS trials, which revealed that the therapeutic removal of immature and mature B cells basically halted development of new inflammatory flares in otherwise relapsing MS patients. This stabilization occurred largely independent of any indirect effect on plasma cell-produced antibody levels. On the contrary, peripherally produced autoantibodies are probably the most important B cell component in two other CNS demyelinating diseases which are currently in the process of being delineated as separate disease entities. The first one is neuromyelitis optica in which an antibody response against aquaporin-4 targets and destroys astrocytes, the second, likely distinct entity embraces a group of patients containing antibodies against myelin oligodendrocyte glycoprotein. In this review, we will describe and summarize pro-inflammatory B cell properties in these three CNS demyelinating disorders; we will however also provide an overview on the emerging concept that B cells or B cell subsets may exert immunologically counterbalancing properties, which may be therapeutically desirable to maintain and foster in inflammatory CNS demyelination. In an outlook, we will discuss accordingly, how this potentially important aspect can be harnessed to advance future B cell-directed therapeutic approaches in multiple sclerosis and related diseases."],["dc.identifier.doi","10.3389/fimmu.2019.00201"],["dc.identifier.pmid","30800132"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15881"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59722"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.publisher","Frontiers Media S.A."],["dc.relation.eissn","1664-3224"],["dc.relation.issn","1664-3224"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject.ddc","610"],["dc.title","The Role of B Cells and Antibodies in Multiple Sclerosis, Neuromyelitis Optica, and Related Disorders."],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","25690"],["dc.bibliographiccitation.issue","41"],["dc.bibliographiccitation.journal","Proceedings of the National Academy of Sciences"],["dc.bibliographiccitation.lastpage","25699"],["dc.bibliographiccitation.volume","117"],["dc.contributor.author","Nissimov, Nitzan"],["dc.contributor.author","Hajiyeva, Zivar"],["dc.contributor.author","Torke, Sebastian"],["dc.contributor.author","Grondey, Katja"],["dc.contributor.author","Brück, Wolfgang"],["dc.contributor.author","Häusser-Kinzel, Silke"],["dc.contributor.author","Weber, Martin S."],["dc.date.accessioned","2021-04-14T08:31:41Z"],["dc.date.available","2021-04-14T08:31:41Z"],["dc.date.issued","2020"],["dc.identifier.doi","10.1073/pnas.2012249117"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/83682"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.relation.eissn","1091-6490"],["dc.relation.issn","0027-8424"],["dc.title","B cells reappear less mature and more activated after their anti-CD20–mediated depletion in multiple sclerosis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Journal of Neuroinflammation"],["dc.bibliographiccitation.volume","16"],["dc.contributor.author","Traub, Jan W."],["dc.contributor.author","Pellkofer, Hannah L."],["dc.contributor.author","Grondey, Katja"],["dc.contributor.author","Seeger, Ira"],["dc.contributor.author","Rowold, Christoph"],["dc.contributor.author","Brück, Wolfgang"],["dc.contributor.author","Husseini, Leila"],["dc.contributor.author","Häusser-Kinzel, Silke"],["dc.contributor.author","Weber, Martin S."],["dc.date.accessioned","2021-06-01T10:48:04Z"],["dc.date.available","2021-06-01T10:48:04Z"],["dc.date.issued","2019"],["dc.description.abstract","Abstract Background In the past, multiple sclerosis (MS) medications have been primarily designed to modulate T cell properties. Based on the emerging concept that B cells are equally important for the propagation of MS, we compared the effect of four commonly used, primarily T cell-targeting MS medications on B cells. Methods Using flow cytometry, we analyzed peripheral blood mononuclear cells (PBMC) of untreated ( n  = 19) and dimethyl fumarate (DMF; n  = 21)-, fingolimod (FTY; n  = 17)-, glatiramer acetate (GA; n  = 18)-, and natalizumab (NAT; n  = 20)-treated MS patients, focusing on B cell maturation, differentiation, and cytokine production. Results While GA exerted minor effects on the investigated B cell properties, DMF and FTY robustly inhibited pro-inflammatory B cell function. In contrast, NAT treatment enhanced B cell differentiation, activation, and pro-inflammatory cytokine production when compared to both intraindividual samples collected before NAT treatment initiation as well as untreated MS controls. Our mechanistic in vitro studies confirm this observation. Conclusion Our data indicate that common MS medications have differential, in part opposing effects on B cells. The observed activation of peripheral B cells upon NAT treatment may be instructive to interpret its unfavorable effect in certain B cell-mediated inflammatory conditions and to elucidate the immunological basis of MS relapses after NAT withdrawal. Trial registration Protocols were approved by the ethical review committee of the University Medical Center Göttingen (#3/4/14)."],["dc.identifier.doi","10.1186/s12974-019-1593-2"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/16681"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/85818"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-425"],["dc.notes.intern","Merged from goescholar"],["dc.relation.eissn","1742-2094"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Natalizumab promotes activation and pro-inflammatory differentiation of peripheral B cells in multiple sclerosis patients"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","9773"],["dc.bibliographiccitation.issue","39"],["dc.bibliographiccitation.journal","Proceedings of the National Academy of Sciences"],["dc.bibliographiccitation.lastpage","9778"],["dc.bibliographiccitation.volume","115"],["dc.contributor.author","Häusler, Darius"],["dc.contributor.author","Häusser-Kinzel, Silke"],["dc.contributor.author","Feldmann, Linda"],["dc.contributor.author","Torke, Sebastian"],["dc.contributor.author","Lepennetier, Gildas"],["dc.contributor.author","Bernard, Claude C. A."],["dc.contributor.author","Zamvil, Scott S."],["dc.contributor.author","Brück, Wolfgang"],["dc.contributor.author","Lehmann-Horn, Klaus"],["dc.contributor.author","Weber, Martin S."],["dc.date.accessioned","2021-06-01T10:51:05Z"],["dc.date.available","2021-06-01T10:51:05Z"],["dc.date.issued","2018"],["dc.description.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."],["dc.identifier.doi","10.1073/pnas.1810470115"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/86889"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-425"],["dc.relation.eissn","1091-6490"],["dc.relation.issn","0027-8424"],["dc.title","Functional characterization of reappearing B cells after anti-CD20 treatment of CNS autoimmune disease"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","5021"],["dc.bibliographiccitation.issue","14"],["dc.bibliographiccitation.journal","International Journal of Molecular Sciences"],["dc.bibliographiccitation.volume","21"],["dc.contributor.author","Traub, Jan"],["dc.contributor.author","Häusser-Kinzel, Silke"],["dc.contributor.author","Weber, Martin"],["dc.date.accessioned","2021-04-14T08:25:04Z"],["dc.date.available","2021-04-14T08:25:04Z"],["dc.date.issued","2020"],["dc.identifier.doi","10.3390/ijms21145021"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/81512"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.relation.eissn","1422-0067"],["dc.title","Differential Effects of MS Therapeutics on B Cells—Implications for Their Use and Failure in AQP4-Positive NMOSD Patients"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]