Primary antibody responses to a well-defined and unique hapten are not enhanced by preimmunization with carrier: analysis in a viral model.

Abstract

We used a viral model to reexamine classical experiments showing that mice previously primed with a "carrier" molecule alone and then challenged with the carrierhapten conjugate exhibited an enhanced antihapten antibody response. Mice were primed with live or UV-inactivated vesicular stomatitis virus (VSV) Indiana (bId) 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.

Antiviral immune responses in gene-targeted mice expressing the immunoglobulin heavy chain of virus-neutralizing antibodies

“…3C). However, in primed WT mice, IgM and IgG titers increased almost simultaneously (35,36). Therefore, the observed delay in isotype class switching in TgH(VI10) mice provided evidence that the additional neutralizing Abs are produced by de novo-activated B cells that were helped by de novo-activated T cells.…”

Memory CD4 T Cells That Express CXCR5 Provide Accelerated Help to B Cells

“…With this in mind, several studies have investigated the contribution of CD4 memory T cells to B cell responses (11-15, 41). These studies have proved inconclusive, providing conflicting results perhaps because they have examined T cell responses in artificial environments and have not addressed a mechanism for any enhanced help that was observed.…”

“…There is some evidence that CD4 memory T cells can provide accelerated help for antibody responses (11-14) however, this may be limited to B cell responses directed towards haptens rather than more relevant antigens (15). More importantly, there is currently no mechanistic information to explain how CD4 memory T cells could provide an enhanced helper response.…”

CD4 memory T cells: What are they and what can they do?

“…Gupta et al asked this question by examining the antibody response in mice primed with one serotype of vesicular stomatitis virus (VSV) and then challenged with a second serotype [113]. This is an example of heterosubtypic immunity in which the two serotypes shared common T cell epitopes but required different antibody responses to neutralize them.…”