Plasma cells in the central nervous system in the Theiler's virus model of multiple sclerosis

Abstract

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.

Methodology: 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.

Significance: 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.