Most knowledge of immunoregulatory mechanisms has been derived from studies of the initial induction of immune responses. By comparison, the mechanisms responsible for the long-term maintenance and regulation of ongoing immune responses have been neglected. Nevertheless, the mechanisms responsible for long-term maintenance and regulation are of major significance. For example, attempts to modulate immune responses are often undertaken in patients with IgE mediated allergy weeks to years after they were initially induced. If immunological intervention is to be done optimally, it is important that we understand how immune responses are maintained and regulated. Our research has focused on the maintenance and regulation of the IgG antibody responses. Although the IgG isotype has been our focus, IgE responses are also maintained for a considerable period and may be maintained using similar mechanisms. Follicular dendritic cells (FDC)-retained antigen and antibody feedback regulation appears to be very important in the maintenance of IgG responses. Our hypothesis is that FDC and antibody feedback regulation play major roles in the maintenance and regulation of IgE responses. WE propose to test this hypothesis. To this end we have four specific aims. 1. We will study specific """"""""spontaneous"""""""" IgE antibody responses and study antibody feedback regulation. (In this proposal """"""""the spontaneous Ab response"""""""" is used to denote the rise in Ab synthesis when lymphoid cells are transferred from immune animals into irradiated recipients or into cell cultures in the absence of added Ag.) 2. We will determine if FDC trap and retain IgE immune complexes and if immune complex coated bodies """"""""iccosomes"""""""" are formed by FDC using IgE containing immune complexes. 3. We will determine if the B cells in the germinal centers from an IgE producing site are committed to IgE production. 4. We will determine if the Fc xi RII on the germinal center B cells in IgE producing sites is superinduced and if it is involved in the uptake and processing of antigen on iccosomes.
