Plasma cells in the central nervous system in the Theiler's virus model of multiple sclerosis.
BACKGROUND
Immunoglobulin production within the central nervous system (CNS) is a prominent feature of multiple sclerosis and its animal model induced by infection with Theiler's meningoencephalitis virus, as well as of other inflammatory and infectious neurological diseases. However, relatively little is known about the plasma cells (PCs) responsible for producing Ig within the CNS.


METHODS
We induced Theiler's-induced demyelinating disease, characterized by disability, inflammation, and demyelination. We used immunofluorescence to localize and characterize IgG-producing cells, and correlated the morphology with results from CSF and tissue analysis.


RESULTS
Confidence that IgG production occurred within the CNS was gained by demonstrating high levels of IgG in the cerebrospinal fluid in the absence of blood-CSF barrier or blood-brain barrier breakdown. CNS IgG-producing cells were CD138+, like IgG-producing cells elsewhere in the body. Less than 5% of IgG-positive cells were Ki67-positive, indicating that most were nonproliferative PCs. The PCs were present primarily in perivascular infiltrates and in the meninges. Isolated PCs could be found in the CNS parenchyma, and, when present, were largely in demyelinated regions of the cord.


CONCLUSIONS
These results demonstrate that PCs are a significant part of this chronic progressive disabling demyelinating disease, and suggest the possibility that these cells play a role in CNS injury by their secretion of immunoglobulin.
UMDNJ-New Jersey Medical School, Department of Neurology and Neuroscience, and Cell Biology and Molecular Medicine, Newark, NJ, United States. pachner@umdnj.edu
Andrew R
AR
Pachner
Libin
L
Li
David
D
Lagunoff
D000818:Animals; D001812:Blood-Brain Barrier / Q000276:immunology / Q000473:pathology; D002469:Cell Separation; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D007074:Immunoglobulin G / Q000097:blood / Q000134:cerebrospinal fluid; D051379:Mice; D018613:Microscopy, Confocal; D009103:Multiple Sclerosis / Q000276:immunology* / Q000473:pathology*; D010950:Plasma Cells / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013116:Spinal Cord / Q000276:immunology* / Q000473:pathology*; D017945:Theilovirus
D007074:Immunoglobulin G