IgE enhances specific antibody and T-cell responses in mice overexpressing CD23.
IgE administered with its specific antigen in vivo induces enhanced proliferation of specific T cells as well as enhanced production of specific antibodies. Both effects are dependent on the low-affinity receptor for IgE (CD23) and the underlying mechanism is thought to be increased antigen presentation following uptake of IgE/antigen complexes via CD23(+) B cells. By contrast, CD23 negatively regulates antibody responses to antigens administered with alum, i.e. without IgE. This effect has been observed as low IgG1 and IgE responses in transgenic mice overexpressing CD23 (CD23Tg). The present study was designed to test whether IgE could enhance antibody and T-cell responses in CD23Tg animals or whether CD23's downregulatory effect precludes IgE-mediated enhancement. IgE-anti-TNP administered with OVA-TNP enhances the OVA-specific antibody responses in wild-type (wt) and CD23Tg mice equally well. Interestingly, the total magnitude of antibody responses to IgE + OVA-TNP and to uncomplexed OVA-TNP, as well as to sheep erythrocytes and keyhole limpet haemocyanine, were lower in the CD23Tg mice. IgE induced proliferation of OVA-specific CD4(+) T cells to the same degree in wt and CD23Tg mice. The effect on T cells was dependent on CD23(+) B cells as demonstrated in in vitro proliferation assays. In conclusion, CD23 does indeed have dual immunoregulatory effects in the same animal. The receptor mediates enhancement of antibody and T-cell responses to IgE-complexed antigen, most likely via increased presentation of complexed antigen, while it negatively regulates the total antibody response to a variety of antigens.
Carlsson
F
F
Department of Genetics and Pathology, Uppsala University, Uppsala, Sweden.
Hjelm
F
F
Conrad
D H
DH
Heyman
B
B
D000818:Animals; D000918:Antibody Specificity / Q000235:genetics; D017951:Antigen Presentation / Q000235:genetics; D002478:Cells, Cultured; D007073:Immunoglobulin E / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D017455:Receptors, IgE / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*
D017455:Receptors, IgE; D007073:Immunoglobulin E