Enhanced and sustained activation of human B cells by anti-immunoglobulin conjugated to the EBV glycoprotein gp350.
We coupled a monoclonal anti-human IgD to the gp350 gylcoprotein of Epstein-Barr virus, which has been shown to bind to the complement receptor 2 (CR2), and compared its B cell stimulatory ability to that of anti-Ig and to a multivalent anti-Ig-dextran conjugate. The anti-Ig-gp350 conjugate stimulated higher levels of human B cell proliferation in vitro than did anti-Ig or anti-Ig conjugated to control viral protein, comparable to the proliferation stimulated by the multivalent anti-Ig-dextran. This enhanced proliferation was dependent on binding of the conjugate to CR2, inasmuch as an anti-CD2 antibody blocked the enhanced proliferative response. This enhanced proliferative response was associated with prolonged elevations of intracellular ionized calcium, which was comparable to the response stimulated by anti-Ig-dextran. These findings suggest the use of gp350 as a carrier molecule for weakly immunogenic peptides or antigens which, when bound to gp350, would enhance B cell clonal expansion and activation of antigen-specific B cells.
Goeckeritz
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BE
Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda 20814, USA.
Lees
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Vos
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Tsokos
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GC
Kuhlbusch
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Mond
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D000888:Antibodies, Anti-Idiotypic / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000956:Antigens, Viral / Q000008:administration & dosage; D001402:B-Lymphocytes / Q000276:immunology*; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D018796:Immunoconjugates / Q000494:pharmacology*; D066298:In Vitro Techniques; D017464:Receptors, Complement 3d / Q000276:immunology; D014763:Viral Matrix Proteins / Q000008:administration & dosage / Q000276:immunology*
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D000956:Antigens, Viral; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D018796:Immunoconjugates; D017464:Receptors, Complement 3d; D014763:Viral Matrix Proteins