Recapitulation of B cell differentiation in the central nervous system of patients with multiple sclerosis

Anna Corcione, Simona Casazza, Elisa Ferretti, Debora Giunti, Emanuela Zappia, Angela Pistorio, Claudio Gambini, Giovanni Luigi Mancardi, Antonio Uccelli, Vito Pistoia

Research output: Contribution to journalArticle

Abstract

Clonally expanded populations of B cells carrying somatic mutations of Ig variable (V) region genes have been detected in the CNS of subjects with multiple sclerosis (MS), suggesting that a process of B cell affinity maturation with ensuing production of potentially pathogenic autoantibodies may occur inside the CNS. Here, we have characterized the B cell subsets present in the cerebrospinal fluid (CSF) of MS patients and of individuals with other inflammatory neurological disorders by flow cytometry. CD19+CD38 high+CD77+, Ki67+, Bcl-2- centroblasts, i.e., a B cell subset found exclusively in secondary lymphoid organs, were detected in the CSF but not in paired peripheral blood from both patient groups. CD27+IgD- memory B cells, i.e., cells with hypermutated IgV genes, were significantly increased in the CSF vs. paired peripheral blood and displayed up-regulation of the CD80 and CD86 costimulatory molecules and of CC chemokine receptor (CCR) 1, CCR2, and CCR4 in both patient groups. Lymphotoxin-α, CXC ligand (CXCL) 12, and CXCL13, key mediators of lymphoid neogenesis, were present in the CSF from patients with MS and other inflammatory neurological disorders and were expressed in MS brain tissue, with selective localization in the outer layer of the capillary vessel wall. In conclusion, this study suggests that a compartmentalized B cell response occurs within the CNS during an ongoing inflammatory reaction, through a recapitulation of all stages of B cell differentiation observed in secondary lymphoid organs. The presence of lymphotoxin-α, CXCL12, and CXCL13 in the CNS may provide favorable microenvironmental conditions for these events.

Original languageEnglish
Pages (from-to)11064-11069
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume101
Issue number30
DOIs
Publication statusPublished - Jul 27 2004

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Multiple Sclerosis
Cell Differentiation
B-Lymphocytes
Central Nervous System
Cerebrospinal Fluid
B-Lymphocyte Subsets
Lymphotoxin-alpha
Nervous System Diseases
CCR1 Receptors
Immunoglobulin Variable Region
Immunoglobulin D
Autoantibodies
Genes
Flow Cytometry
Up-Regulation
Ligands
Mutation
Brain
Population

ASJC Scopus subject areas

  • Genetics
  • General

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Recapitulation of B cell differentiation in the central nervous system of patients with multiple sclerosis. / Corcione, Anna; Casazza, Simona; Ferretti, Elisa; Giunti, Debora; Zappia, Emanuela; Pistorio, Angela; Gambini, Claudio; Mancardi, Giovanni Luigi; Uccelli, Antonio; Pistoia, Vito.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 101, No. 30, 27.07.2004, p. 11064-11069.

Research output: Contribution to journalArticle

Corcione, Anna ; Casazza, Simona ; Ferretti, Elisa ; Giunti, Debora ; Zappia, Emanuela ; Pistorio, Angela ; Gambini, Claudio ; Mancardi, Giovanni Luigi ; Uccelli, Antonio ; Pistoia, Vito. / Recapitulation of B cell differentiation in the central nervous system of patients with multiple sclerosis. In: Proceedings of the National Academy of Sciences of the United States of America. 2004 ; Vol. 101, No. 30. pp. 11064-11069.
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