Universität zu Köln

Kuerten, Stefanie, Schickel, Achim, Kerkloh, Christian, Recks, Mascha S., Addicks, Klaus, Ruddle, Nancy H. and Lehmann, Paul V. (2012). Tertiary lymphoid organ development coincides with determinant spreading of the myelin-specific T cell response. Acta Neuropathol., 124 (6). S. 861 - 874. NEW YORK: SPRINGER. ISSN 0001-6322

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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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Kuerten, Stefanie UNSPECIFIED UNSPECIFIED UNSPECIFIED Schickel, Achim UNSPECIFIED UNSPECIFIED UNSPECIFIED Kerkloh, Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED Recks, Mascha S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Addicks, Klaus UNSPECIFIED UNSPECIFIED UNSPECIFIED Ruddle, Nancy H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Lehmann, Paul V. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-477586
DOI:	10.1007/s00401-012-1023-3
Journal or Publication Title:	Acta Neuropathol.
Volume:	124
Number:	6
Page Range:	S. 861 - 874
Date:	2012
Publisher:	SPRINGER
Place of Publication:	NEW YORK
ISSN:	0001-6322
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; PROGRESSIVE MULTIPLE-SCLEROSIS; CENTRAL-NERVOUS-SYSTEM; GERMINAL-CENTERS; MENINGEAL INFLAMMATION; CORTICAL DEMYELINATION; C57BL/6 MICE; B-CELLS; PATHOLOGY; NEOGENESIS Multiple languages Clinical Neurology; Neurosciences; Pathology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/47758