Virus-specific antibody, in the absence of T cells, mediates demyelination in mice infected with a neurotropic coronavirus.
Mice infected with mouse hepatitis virus strain JHM develop an inflammatory demyelinating disease in the central nervous system with many similarities to human multiple sclerosis. The mouse disease is primarily immune-mediated because demyelination is not detected in JHM-infected mice lacking T or B cells but does occur after transfer of JHM-specific T cells. Although less is known about the ability of antibodies to mediate demyelination, the presence of oligoclonally expanded B cells and high concentrations of antibodies (against self or infectious agents) in the central nervous system of many multiple sclerosis patients suggests that antibodies may also contribute to myelin destruction. Here, we show that anti-JHM antibodies, in the absence of T or B cells, caused demyelination in JHM-infected mice. Anti-JHM antibody was detected adjacent to areas of demyelination, consistent with a direct interaction between antibody and infected cells. Demyelination was reduced by 85 to 90% in infected RAG1(-/-) mice lacking normal expression of activating Fc receptors (FcRgamma(-/-)) and by approximately 76% when complement was depleted by treatment with cobra venom factor. These data demonstrate that JHM-specific antibodies are sufficient to cause demyelination and that myelin destruction in the presence of anti-virus antibodies results from a combination of complement- and Fc receptor-dependent mechanisms.
Kim
Taeg S
TS
Interdisciplinary Program in Immunology, University of Iowa, Iowa City, IA 52242, USA.
Perlman
Stanley
S
D000818:Animals; D015704:CD4 Antigens / Q000096:biosynthesis; D004396:Coloring Agents / Q000494:pharmacology; D003165:Complement System Proteins; D017934:Coronavirus / Q000276:immunology*; D003711:Demyelinating Diseases / Q000276:immunology*; D007150:Immunohistochemistry; D007211:Indoles / Q000494:pharmacology; D007700:Kinetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D009186:Myelin Sheath / Q000737:chemistry / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*; D013997:Time Factors
D015704:CD4 Antigens; D004396:Coloring Agents; D007211:Indoles; C018588:Luxol Fast Blue MBS; D003165:Complement System Proteins
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