N-glycans on the short ectodomain of the primary envelope glycoprotein play a major role in the polyclonal activation of B cells by lactate dehydrogenase-elevating virus.
The common biologically cloned isolates of lactate dehydrogenase-elevating virus (LDV-P and LDV-vx) invariably cause a polyclonal activation of B cells in immunocompetent mice. It is recognized by an at least 10-fold increase in plasma IgG2a levels and the de novo formation of immune complexes that most likely consist of autoantibodies and their antigens. The present study indicates that three closely spaced N-glycans on the short ectodomain of the primary envelope glycoprotein, VP-3P, of LDV-P/vx, play a major role in inducing the polyclonal proliferation of B cells. IFN-gamma then seems to mediate the differentiation of the activated B cells to IgG2a-producing plasma cells. These conclusions are based on the finding that the IgG2a hypergammaglobulinaemia and immune complex formation were much lower in mice that were infected with LDV variants (LDV-C and LDV-v) whose VP-3P ectodomains lack two of the three N-glycans than in LDV-P/vx infected mice. In contrast, the VP-3P ectodomains of three neutralization escape variants of LDV-C/v whose VP-3P ectodomains possess three N-glycosylation sites caused a polyclonal activation of B cells comparable to that of LDV-P/vx.
Plagemann
Peter G W
PGW
Department of Microbiology, University of Minnesota, Minneapolis, MN 55455, USA1.
Jones
Quentin A
QA
Division of Basic Biomedical Sciences, Molecular Microbiology & Immunology Group, University of South Dakota School of Medicine, Vermillion, SD 57069, USA2.
Cafruny
William A
WA
Division of Basic Biomedical Sciences, Molecular Microbiology & Immunology Group, University of South Dakota School of Medicine, Vermillion, SD 57069, USA2.
D000595:Amino Acid Sequence; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D015686:Gene Products, env / Q000737:chemistry*; D006031:Glycosylation; D007074:Immunoglobulin G / Q000096:biosynthesis; D007770:L-Lactate Dehydrogenase / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D011134:Polysaccharides / Q000276:immunology*; D013329:Structure-Activity Relationship; D014759:Viral Envelope Proteins / Q000276:immunology; D014766:Viremia / Q000276:immunology
D015686:Gene Products, env; D007074:Immunoglobulin G; C096094:M-VP-2 protein, lactate dehydrogenase-elevating virus; D008562:Membrane Glycoproteins; D011134:Polysaccharides; C096091:VP-3 protein, lactate dehydrogenase-elevating virus; D014759:Viral Envelope Proteins; D007770:L-Lactate Dehydrogenase