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 cell s 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 t he 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 m ediate the differentiation of the activated B cells to IgG2a-producing plas ma cells, These conclusions are based on the finding that the IgG2a hyperga mmaglobulinaemia and immune complex formation were much lower in mice that were infected with LDV variants (LDV-C and LDV-V) whose VP-3P ectodomains l ack 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 w hose VP-3P ectodomains possess three N-glycosylation sites caused a polyclo nal activation of B cells comparable to that of LDV-P/vx.