Early Immunostimulatory Effects of IgE- and IgG Antibodies

Detta är en avhandling från Uppsala : Acta Universitatis Upsaliensis

Sammanfattning: 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 Fc?RI. We re-examined the role of this receptor in a new mouse strain completely lacking Fc?RI 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.