Primary antibody responses to a well-defined and unique hapten are not enhanced by preimmunization with carrier: analysis in a viral model.
We used a viral model to reexamine classical experiments showing that mice previously primed with a "carrier" molecule alone and then challenged with the carrier-hapten conjugate exhibited an enhanced antihapten antibody response. Mice were primed with live or UV-inactivated vesicular stomatitis virus (VSV) Indiana (Ind) serotype with or without complete Freund's adjuvant. After challenge with VSV New Jersey (NJ), these mice developed a secondary-type IgG response, measured by antibody binding in an ELISA, against both VSV-Ind and VSV-NJ. The same result was found for the reciprocal experiments where mice were primed with VSV-NJ. Similarly, when mice were primed with live VSV, UV-inactivated VSV, or purified VSV glycoprotein G of Ind or NJ serotype and later were challenged with dinitrophenyl (N2ph)-conjugated, UV-inactivated VSV or with N2ph-conjugated G protein of either serotype, they exhibited a secondary-type anti-N2ph antibody response as demonstrated by the binding of IgG to dinitrophenylated bovine serum albumin measured by ELISA. In contrast, when neutralizing antibody responses were monitored, VSV-Ind-primed mice challenged with VSV-NJ developed a strictly primary type of anti-VSV-NJ response and vice versa. We conclude that preexistent helper T cells specific for shared carrier determinants do not improve virgin B-cell responses specific for "new," unique determinants that are the target for the biologically relevant neutralizing antibodies. These findings suggest that priming of B cells rather than of helper T cells may be of importance to induce protective immunity mediated by antibodies.
D000818:Animals; D000917:Antibody Formation; D000918:Antibody Specificity; D000956:Antigens, Viral / Q000276:immunology; D004136:Dinitrobenzenes / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D006241:Haptens; D007074:Immunoglobulin G / Q000096:biosynthesis; D007156:Immunologic Memory; D008562:Membrane Glycoproteins; D051379:Mice; D008811:Mice, Inbred DBA; D009578:Nitrobenzenes / Q000276:immunology*; D014721:Vesicular stomatitis Indiana virus / Q000276:immunology*; D018116:Vesiculovirus; D014759:Viral Envelope Proteins; D014764:Viral Proteins / Q000276:immunology
D000956:Antigens, Viral; D004136:Dinitrobenzenes; C028391:G protein, vesicular stomatitis virus; D006241:Haptens; D007074:Immunoglobulin G; D008562:Membrane Glycoproteins; D009578:Nitrobenzenes; D014759:Viral Envelope Proteins; D014764:Viral Proteins