Polyclonal Activation of B Cells by Lactate Dehydrogenase-Elevating Virus is Mediated by N-Glycans on the Short Ectodomain of the Primary Envelope Glycoprotein
The common strains of lactate dehydrogenase-elevating virus (LDV-P and LD-vx) are primary examples for viruses that cause a permanent polyclonal activation of B cells that results in IgG2a hyper-gammaglobulinemia and the generation of autoantibodies and circulating immune complexes in their host, the mouse (Notkins et al., 1966; Coutelier and van Snick, 1985; Li et al, 1990). Plasma IgG2a levels increase from generally below 0.5 mg/ml to 2-6 mg/ml by two weeks post infection (p.i.) and remain elevated thereafter (see later). LDV-P/vx cause life-long persistent viremic infections (see Fig. 1A) which are maintained by continuous rounds of replication in a renewable subpopulation of macrophages and resistance to host immune responses (Plagemann, 1996). Previous results have shown that the single neutralization epitope located on the short (about 30 amino acids long) ectodomain of the primary envelope glycoprotein, VP-3P, carries three large N-glycan chains in LDV-P and LDV-vx (see Fig. 1A insert) that suppress the immunogenicity of the epitope and impair antibody neutralization of the virions of these quasispecies (Chen et al, 2000; Plagemann et al., 1999). The present results indicate that the three N-glycans on the VP-3P ectodomains of LDV-P/vx also play a critical role in the polyclonal activation of B cells by these LDVs.
KeywordsImmune Complex Infected Mouse Antiviral Immune Response Immune Complex Formation Polyclonal Activation
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