title: Central nervous system infiltrates are characterized by features of ongoing B cell-related immune activity in MP4-induced experimental autoimmune encephalomyelitis.
abstract: In multiple sclerosis (MS) lymphoid follicle-like aggregates have been reported in the meninges of patients. Here we investigated the functional relevance of B cell infiltration into the central nervous system (CNS) in MP4-induced experimental autoimmune encephalomyelitis (EAE), a B cell-dependent mouse model of MS. In chronic EAE, B cell aggregates were characterized by the presence of CXCL13(+) and germinal center CD10(+) B cells. Germline transcripts were expressed in the CNS and particularly related to TH17-associated isotypes. We also observed B cells with restricted VH gene usage that differed from clones found in the spleen. Finally, we detected CNS-restricted spreading of the antigen-specific B cell response towards a myelin and a neuronal autoantigen. These data imply the development of autonomous B cell-mediated autoimmunity in the CNS in EAE - a concept that might also apply to MS itself.
authors: Department of Anatomy I, University of Cologne, Joseph-Stelzmann-Str. 9, 50931 Cologne, Germany.
authors: Helena
authors: H
authors: Batoulis
authors: Department of Anatomy and Cell Biology, University of Wuerzburg, Koellikerstr. 6, 97070 Wuerzburg, Germany.
authors: Marie
authors: M
authors: Wunsch
authors: Department of Anatomy I, University of Cologne, Joseph-Stelzmann-Str. 9, 50931 Cologne, Germany.
authors: Johannes
authors: J
authors: Birkenheier
authors: Department of Anatomy and Cell Biology, University of Wuerzburg, Koellikerstr. 6, 97070 Wuerzburg, Germany.
authors: Andrea
authors: A
authors: Rottlaender
authors: Department of Anatomy and Cell Biology, University of Wuerzburg, Koellikerstr. 6, 97070 Wuerzburg, Germany.
authors: Valentin
authors: V
authors: Gorboulev
authors: Department of Anatomy and Cell Biology, University of Wuerzburg, Koellikerstr. 6, 97070 Wuerzburg, Germany. Electronic address: stefanie.kuerten@uni-wuerzburg.de.
authors: Stefanie
authors: S
authors: Kuerten
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D002490:Central Nervous System / Q000276:immunology*; D002531:Cerebellum / Q000276:immunology / Q000378:metabolism; D054382:Chemokine CXCL13 / Q000276:immunology; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D051379:Mice; D009103:Multiple Sclerosis / Q000276:immunology*; D004676:Myelin Basic Protein / Q000276:immunology; D018991:Myelin Proteolipid Protein / Q000276:immunology; D009186:Myelin Sheath / Q000276:immunology*; D015260:Neprilysin / Q000276:immunology; D012333:RNA, Messenger / Q000378:metabolism*; D013154:Spleen / Q000276:immunology / Q000378:metabolism
chemical_list: D001324:Autoantigens; D054382:Chemokine CXCL13; C486386:Cxcl13 protein, mouse; D004676:Myelin Basic Protein; D018991:Myelin Proteolipid Protein; D012333:RNA, Messenger; D015260:Neprilysin
keywords: B cells; EAE; Epitope spreading; MS; TLO