Theiler's virus-induced demyelination in mice immunosuppressed with anti-IgM and in mice expressing the xid gene.
Intracerebral infection with Theiler's murine encephalomyelitis virus produces chronic immune-mediated demyelination in susceptible strains of mice. We examined the role of Ig in the pathogenesis of demyelination. In susceptible SJL/J mice (H-2s), suppression of B cell responses with IgG fraction of goat anti-mu (anti-mu IgG) from birth resulted in increased numbers and severity of demyelinating lesions in the spinal cord 35 days after infection. In contrast, treatment of resistant C57BL/10 (H-2b), C57BL/6 (H-2b), or B10.D2 (H-2d) mice with anti-mu IgG had no apparent effect since these mice did not develop demyelination or inflammation in the spinal cord following infection. Similar results were obtained with certain strains of B-cell deficient mice that exhibit the xid gene mutation. Male CBA/NJ (xid) showed increased meningeal inflammation and demyelination compared to male CBA/J mice. However, B6.CBAN, C3.CBAN, or C.CBAn mice showed no or minimal evidence of demyelination despite the presence of the xid mutation. In the SJL/J mouse, the majority of the humoral immune response to virus antigen was restricted to the IgG2b and IgM isotypes. These data indirectly support the hypothesis that immunoglobulins protect partially against development of virus-induced demyelination in susceptible but not resistant animals. In addition, the data argue strongly against the hypothesis that TMEV-induced demyelination is mediated predominantly by humoral autoimmune or humoral viral immune mechanisms.
Rodriguez
M
M
Department of Neurology and Immunology, Mayo Medical School, Rochester, MN 55905.
Kenny
J J
JJ
Thiemann
R L
RL
Woloschak
G E
GE
D000818:Animals; D000888:Antibodies, Anti-Idiotypic; D003711:Demyelinating Diseases / Q000235:genetics / Q000276:immunology* / Q000382:microbiology; D004406:Dysgammaglobulinemia / Q000150:complications* / Q000235:genetics; D004769:Enterovirus Infections / Q000235:genetics / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D015870:Gene Expression; D007074:Immunoglobulin G / Q000378:metabolism; D007075:Immunoglobulin M / Q000172:deficiency* / Q000235:genetics / Q000276:immunology; D007153:Immunologic Deficiency Syndromes / Q000150:complications* / Q000235:genetics; D004680:Maus Elberfeld virus; D051379:Mice; D009154:Mutation
D000888:Antibodies, Anti-Idiotypic; D007074:Immunoglobulin G; D007075:Immunoglobulin M