Regulation of immune complexes during infection of mice with lactate dehydrogenase-elevating virus: studies with interferon-gamma gene knockout and tolerant mice.
Mice persistently infected with lactate dehydrogenase-elevating virus (LDV) develop circulating IgG-containing hydrophobic immune complexes, with a molecular mass of 150 to 300 kd, which bind to the surfaces of high-capacity enzyme-linked immunosorbent assay (ELISA) plates. LDV infection also stimulates polyclonal B-cell activation and autoimmunity. For this study, interferon-gamma gene knockout (GKO) mice were utilized to study circulating immune complexes and other parameters of LDV infection. The kinetics of LDV viremia, formation of plasma IgG anti-LDV antibodies, and LDV replication in the spleen and liver were essentially normal in GKO mice. Polyclonal activation of B cells, as reflected by increased total plasma IgG concentration during LDV infection, was found to be intact in GKO mice, although at a lower magnitude than in control mice. The plasma concentration of IgG-containing hydrophobic immune complexes was reduced about 75% in LDV-infected GKO mice relative to normal LDV-infected controls. Allogeneic tissue responses were also found to be reduced in LDV-infected GKO mice relative to those in normal LDV-infected controls. These results dissociate specific anti-LDV immunity from formation of hydrophobic immune complexes, show that the IgG anti-LDV response as well as LDV replication in the spleen and liver are insensitive to physiological levels of interferon (IFN)-gamma, and suggest that IgG-containing immune complexes stimulated by LDV infection are a marker for autoimmunity.
Department of Microbiology, University of South Dakota School of Medicine, Vermillion 57069, USA. bcafruny@usd.edu
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Cafruny
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Bradley
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Rowland
D000818:Animals; D000831:Animals, Newborn; D000914:Antibodies, Viral / Q000097:blood; D000936:Antigen-Antibody Complex / Q000276:immunology*; D018174:Arterivirus Infections / Q000276:immunology* / Q000821:virology; D007108:Immune Tolerance / Q000276:immunology*; D007074:Immunoglobulin G / Q000097:blood; D017403:In Situ Hybridization; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology*; D007772:Lactate dehydrogenase-elevating virus / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D014766:Viremia; D014779:Virus Replication
D000914:Antibodies, Viral; D000936:Antigen-Antibody Complex; D007074:Immunoglobulin G; D007371:Interferon-gamma