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Cited by 1,208Multiple Sclerosis Research StudiesT-cell and B-cell ImmunologyNeuroinflammation and Neurodegeneration Mechanisms

Detection of ectopic B-cell follicles with germinal centers in the meninges of patients with secondary progressive multiple sclerosis.

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Serafini, Barbara, Rosicarelli, Barbara, Magliozzi, Roberta, Stigliano, Egidio, Aloisi, Francesca·2004·Brain Pathology
DOI 10.1111/j.1750-3639.2004.tb00049.xPMC PMC8095922
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Abstract

Multiple sclerosis (MS) is characterized by synthesis of oligoclonal immunoglobulins and the presence of B-cell clonal expansions in the central nervous system (CNS). Because ectopic lymphoid tissue generated at sites of chronic inflammation is thought to be important in sustaining immunopathological processes, we have investigated whether structures resembling lymphoid follicles could be identified in the CNS of MS patients. Sections from post-mortem MS brains and spinal cords were screened using immunohistochemistry for the presence of CD20+ B-cells, CD3+ T-cells, CD138+ plasma cells and CD21+, CD35+ follicular dendritic cells, and for the expression of lymphoid chemokines (CXCL 13, CCL21) and peripheral node addressin (PNAd). Lymphoid follicle-like structures containing B-cells, T-cells and plasma cells, and a network of follicular dendritic cells producing CXCL13 were observed in the cerebral meninges of 2 out of 3 patients with secondary progressive MS, but not in relapsing remitting and primary progressive MS. We also show that proliferating B-cells are present in intrameningeal follicles, a finding which is suggestive of germinal center formation. No follicle-like structures were detected in parenchymal lesions. The formation of ectopic lymphoid follicies in the meninges of patients with MS could represent a critical step in maintaining humoral autoimmunity and in disease exacerbation.

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  1. [7]7. Bofill M, Akbar AN, Amlot PL (2000) Follicular dendritic cells share a membrane‐bound protein with fibroblasts. J Pathol 191:217–226. [DOI] [PubMed] [Google Scholar]
  2. [23]23. Liu YJ, Banchereau J (1996) The paths and molecular controls of peripheral B‐cell development. Immunologist 4:55–66. [Google Scholar]
  3. [31]31. Niehaus A, Shi J, Grzenkowski M, Diers‐Fenger M, Archelos J, Hartung HP, Toyka K, Bruck W, Trotter J (2000) Patients with active relapsing‐remitting multiple sclerosis synthesize antibodies recognizing oligodendrocyte progenitor cell surface protein: implications for remyelination. Ann Neurol 48:362–371. [PubMed] [Google Scholar]
  4. [43]43. Raine CS, Cannella B, Hauser SL, Genain CP (1999) Demyelination in primate autoimmune encephalomyelitis and acute multiple sclerosis lesions: a case for antigen‐specific antibody mediation. Ann Neurol 46:144–160. [DOI] [PubMed] [Google Scholar]
  5. [46]46. Ruddle NH (1999) Lymphoid neo‐organogenesis: lymphotoxin's role in inflammation and development. Immunol Res 19:119–125. [DOI] [PubMed] [Google Scholar]
  6. [55]55. Uccelli A, Concione A, Ferretti E, Giunti D, Zappia E, Fais F, Casazza S, Garello L, Mancardi GL, Pistoia V (2003) A full maturation process of B‐cells into the CSF suggests the existence of in‐trathecal lymphoid‐like compartment in subjects with multiple sclerosis and other inflammatory disorders of the central nervous system. Multiple Sclerosis 9:S66. [Google Scholar]

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Authors
Serafini, B., Rosicarelli, B., Magliozzi, R., Stigliano, E., & Aloisi, F.
Affiliations
  • Istituto Superiore di Sanità (IT)
  • Agostino Gemelli University Polyclinic (IT)
Corresponding author
Aloisi, Francesca
ORCID
Venue
Brain Pathology
Publisher
Wiley
Published
2004-04
Volume
14
Issue
2
Pages
164-174
ISSN
  • 1015-6305 (ISSN-L)
  • 1750-3639
DOI
10.1111/j.1750-3639.2004.tb00049.x
PMC
PMC8095922
OpenAlex
W2118818657
Cited by
1,208
References
61
Citations by year
2026: 39 · 2025: 29 · 2024: 53 · 2023: 70 · 2022: 65 · 2021: 90 · 2020: 63 · 2019: 61 · 2018: 68 · 2017: 60 · 2016: 72 · 2015: 65 · 2014: 67 · 2013: 64 · 2012: 64
FWCI
20.77
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor, 734 d)
Locations
  • Brain Pathology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
secondary progressive multiple sclerosis, germinal center, meninges, B cell follicles, follicular dendritic cells, CXCL13, CCL21, peripheral node addressin, plasma cells, CD20+ B cells, humoral autoimmunity, disease exacerbation, oligoclonal immunoglobulins
MeSH terms
Adult, Aged, Aged, 80 and over, B-Lymphocytes, Brain, Choristoma, Female, Humans, Immunohistochemistry, Male, Meninges, Middle Aged, Multiple Sclerosis, Plasma Cells, Spinal Cord, T-Lymphocytes, Cytokines, Germinal Center, Dendritic Cells, Follicular

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