Journal
BRAIN
Volume 134, Issue -, Pages 534-541Publisher
OXFORD UNIV PRESS
DOI: 10.1093/brain/awq350
Keywords
multiple sclerosis; B cells; clonal expansion; antigen experience; central nervous system
Categories
Funding
- Fondazione Italiana Sclerosi Multipla [FISM-Cod. 2008/B/3]
- Jacob Javits Neuroscience Investigator Merit Award [R37 NS024247]
- US National Institutes of Health [P01AI39671]
- National Multiple Sclerosis Society [RG2172C9, RG3308A10]
- National Health and Medical Research Council of Australia
- UK Medical Research Council [G0700356]
- MRC [G0700356] Funding Source: UKRI
- Medical Research Council [G0700356] Funding Source: researchfish
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In the central nervous system of patients with multiple sclerosis, B cell aggregates populate the meninges, raising the central question as to whether these structures relate to the B cell infiltrates found in parenchymal lesions or instead, represent a separate central nervous system immune compartment. We characterized the repertoires derived from meningeal B cell aggregates and the corresponding parenchymal infiltrates from brain tissue derived primarily from patients with progressive multiple sclerosis. The majority of expanded antigen-experienced B cell clones derived from meningeal aggregates were also present in the parenchyma. We extended this investigation to include 20 grey matter specimens containing meninges, 26 inflammatory plaques, 19 areas of normal appearing white matter and cerebral spinal fluid. Analysis of 1833 B cell receptor heavy chain variable region sequences demonstrated that antigen-experienced clones were consistently shared among these distinct compartments. This study establishes a relationship between extraparenchymal lymphoid tissue and parenchymal infiltrates and defines the arrangement of B cell clones that populate the central nervous system of patients with multiple sclerosis.
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