IgE antibodies, administered to mice together with their specific antigen, enhance antibody and CD4+ T cell responses to this antigen. The effect is dependent on the low affinity receptor for IgE, CD23, and the receptor must be expressed on B cells. In vitro, IgE-antigen complexes are endocytosed via CD23 on B cells, which subsequently present the antigen to CD4+ T cells. This mechanism has been suggested to explain also IgE-mediated enhancement of immune responses in vivo. We recently found that CD23+ B cells capture IgE-antigen complexes in peripheral blood and rapidly transport them to B cell follicles in the spleen. This provides an alternative explanation for the requirement for CD23+ B cells. The aim of the present study was to determine whether B-cell mediated antigen presentation of IgE-antigen complexes explains the enhancing effect of IgE on immune responses in vivo. The ability of spleen cells, taken from mice 1–4 h after immunization with IgE-antigen, to present antigen to specific CD4+ T cells was analyzed. Antigen presentation was intact when spleens were depleted of CD19+ cells (i.e., primarily B cells) but was severely impaired after depletion of CD11c+ cells (i.e., primarily dendritic cells). In agreement with this, the ability of IgE to enhance proliferation of CD4+ T cells was abolished in CD11c-DTR mice conditionally depleted of CD11c+ cells. Finally, the lack of IgE-mediated enhancemen of CD4+ T cell responses in CD23-/- mice could be rescued by transfer of MHC-II-compatible as well as by MHC-II-incompatible CD23+ B cells. These findings argue against the idea that IgE-mediated enhancement of specific CD4+ T cell responses in vivo is caused by increased antigen presentation by B cells. A model where CD23+ B cells act as antigen transporting cells, delivering antigen to CD11c+ cells for presentation to T cells is consistent with available experimental data.

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Influenza viruses remain a major threat to global health due to their ability to undergo change through antigenic drift and antigenic shift. We postulated that avian IgY antibodies represent a low-cost, effective, and well-tolerated approach that can easily be scaled up to produce enormous quantities of protective antibodies. These IgY antibodies can be administered passively in humans (orally and intranasally) and can be used quickly and safely to help in the fight against an influenza pandemic. In this study, we raised IgY antibodies against H1N1, H3N2, and H5N1 influenza viruses. We demonstrated that, using whole inactivated viruses alone and in combination to immunize hens, we were able to induce a high level of anti-influenza virus IgY in the sera and eggs, which lasted for at least 2 months after two immunizations. Furthermore, we found that by use of in vitro assays to test for the ability of IgY to inhibit hemagglutination (HI test) and virus infectivity (serum neutralization test), IgYs inhibited the homologous as well as in some cases heterologous clades and strains of viruses. Using an in vivo mouse model system, we found that, when administered intranasally 1 h prior to infection, IgY to H5N1 protected 100% of the mice against lethal challenge with H5N1. Of particular interest was the finding that IgY to H5N1 cross-protected against A/Puerto Rico/8/34 (H1N1) both in vitro and in vivo. Based on our results, we conclude that anti-influenza virus IgY can be used to help prevent influenza virus infection.

Growth factors contained in Con A(concanavalin A)-conditioned media (CM) maintain exponential growth in T cell blasts derived from mitogen stimulation of spleen cells with Con A, phytohemagglutinin, lentil lectin and pokeweed mitogen (PWM), as well as from mixed lymphocyte reactions to H-2D or I-C-encoded determinants and from non-H-2 Mls locus-controlled reactions. Such growth factors are strictly T cell blast-specific, inasmuch as they do not stimulate resting, small T or B lymphocytes nor B cell blasts generated by lipopolysaccharide or lipoprotein activation. The responsiveness of T cell blasts to CM appears to be the result of the availability on the cell surface of an acceptor site for growth factors which is not expressed in resting cells, because T cell blasts, but not small spleen cells, absorb out the growth-promoting activity contained in CM. Furthermore, lectins such as Con A and PWM interfere with the blast surface membrane in such a way that they inhibit the response to growth factors. Finally, there is no detectable allotypic or isotypic restriction in the activity of Con A-CM on a variety of target T cell blasts.