title: Tertiary lymphoid organ development coincides with determinant spreading of the myelin-specific T cell response.
abstract: While the role of T cells has been studied extensively in multiple sclerosis (MS), the pathogenic contribution of B cells has only recently attracted major attention, when it was shown that B cell aggregates can develop in the meninges of a subset of MS patients and were suggested to be correlates of late-stage and more aggressive disease in this patient population. However, whether these aggregates actually exist has subsequently been questioned and their functional significance has remained unclear. Here, we studied myelin basic protein (MBP)-proteolipid protein (PLP)-induced experimental autoimmune encephalomyelitis (EAE), which is one of the few animal models for MS that is dependent on B cells. We provide evidence that B cell aggregation is reflective of lymphoid neogenesis in the central nervous system (CNS) in MBP-PLP-elicited EAE. B cell aggregation was present already few days after disease onset. With disease progression CNS B cell aggregates increasingly displayed the phenotype of tertiary lymphoid organs (TLOs). Our results further imply that these TLOs were not merely epiphenomena of the disease, but functionally active, supporting intrathecal determinant spreading of the myelin-specific T cell response. Our data suggest that the CNS is not a passive "immune-privileged" target organ, but rather a compartment, in which highly active immune responses can perpetuate and amplify the autoimmune pathology and thereby autonomously contribute to disease progression.
authors: Department of Anatomy I, University of Cologne, Cologne, Germany. stefanie.kuerten@uk-koeln.de
authors: Stefanie
authors: S
authors: Kuerten
authors: Achim
authors: A
authors: Schickel
authors: Christian
authors: C
authors: Kerkloh
authors: Mascha S
authors: MS
authors: Recks
authors: Klaus
authors: K
authors: Addicks
authors: Nancy H
authors: NH
authors: Ruddle
authors: Paul V
authors: PV
authors: Lehmann
mesh_terms: D000818:Animals; D002490:Central Nervous System / Q000276:immunology / Q000473:pathology; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000473:pathology; D005260:Female; D008221:Lymphoid Tissue / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009103:Multiple Sclerosis / Q000276:immunology / Q000473:pathology; D004676:Myelin Basic Protein / Q000276:immunology / Q000378:metabolism; D018991:Myelin Proteolipid Protein / Q000276:immunology / Q000378:metabolism*; D009186:Myelin Sheath / Q000276:immunology* / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology
chemical_list: D004676:Myelin Basic Protein; D018991:Myelin Proteolipid Protein