Abstract
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.
Highlights
Apart from initiating various defense mechanisms via Fcreceptor binding or complement activation, antibodies have the capacity to regulate the immune responses against the antigen they are specific for [1]
CD11c+ cells present IgE-antigen to CD4+ T cells ex vivo To investigate whether bone marrow derived cells (B cells) (CD19+) or CD11c+ cells present IgE-antigen complexes in vivo, mice were immunized with OVA-TNP alone or together with IgE-anti-TNP
Spleen cells depleted of B cells (CD192) were efficient as unfractionated spleen cells, whereas spleen cells depleted of CD11c+ cells (CD11c2) completely lost their antigen presenting capacity, B cells were present in this population (Figure 1A)
Summary
Apart from initiating various defense mechanisms via Fcreceptor binding or complement activation, antibodies have the capacity to regulate the immune responses against the antigen they are specific for [1]. The CD23b isoform has been found on enterocytes in the intestine and recently on lung epithelial cells [19,20] It is well established by several independent groups that human as well as mouse B cells take up IgE-antigen complexes via CD23 and present the antigenic peptides to CD4+ T cells in vitro [21,22,23,24,25]. IgE-antigen was found on the majority of B cells in the blood ten minutes after immunization and were detected in the splenic follicles on CD23hiCD21dim cells (follicular B cells) after 30 minutes [15] This observation provided an alternative explanation for the requirement of CD23+ B cells, suggesting that the enhancing effect of IgE on immune responses could be caused by concentrating the antigen to B cell follicles. The results argue against the idea that presentation of IgE-antigen by CD23+ B cells is the explanation for IgE-mediated enhancement of CD4+ T cell responses in vivo
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