Antibodies have the ability to influence their own production in a process called antibody feedback regulation. Depending on the type of antigen and the subclass of the antibody, the outcome of feedback regulation can be complete suppression or several hundred-fold enhancement of the antibody response. IgE and IgG3 enhance responses to soluble protein antigens. Previous results suggest that IgG3-mediated enhancement of antibody responses is dependent on complement and not Fc receptors for IgG. However, the Fc receptor-deficient animals used did not completely lack the IgG3-binding FcγRI. We re-examined the role of this receptor in a new mouse strain completely lacking FcγRI and found that IgG3-mediated enhancement was unperturbed, thus confirming a role for complement. To investigate the early responses resulting in IgE-mediated enhancement of antibody responses we used biotinylated antigen and found that mature follicular B cells and to a lesser extent transitional type 2 B cells capture IgE/antigen complexes. Adoptive transfer of CD4+ T cells expressing a transgenic TCR specific for ovalbumin demonstrated that these T cells localize near the B-cell follicle after 6-12 hours and that IgE, in contrast to IgG3, significantly increased specific T cell proliferation. After 3 days the T cells had gone through several rounds of divisions and showed an activated phenotype. Additional cell transfer studies identified CD23+ B cells as the responsible effector cells. These results indicate that the mechanism underlying IgE-mediated enhancement is rapid transport of IgE/antigen complexes by follicular B cells into B-cell follicles, followed by antigen presentation by CD23+ B cells to naïve CD4+ T cells. IgG3, inducing poor T cell responses, is more likely to depend on lowering the threshold for B-cell activation by co-ligating the B-cell receptor with the complement receptor 2/CD19 complex on the surface of the B cell.
| Identifer | oai:union.ndltd.org:UPSALLA1/oai:DiVA.org:uu-7209 |
| Date | January 2006 |
| Creators | Hjelm, Fredrik |
| Publisher | Uppsala universitet, Institutionen för genetik och patologi, Uppsala : Acta Universitatis Upsaliensis |
| Source Sets | DiVA Archive at Upsalla University |
| Language | English |
| Detected Language | English |
| Type | Doctoral thesis, comprehensive summary, info:eu-repo/semantics/doctoralThesis, text |
| Format | application/pdf |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, 1651-6206 ; 189 |
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