B cells play a crucial role in the presentation of antigens to CD4+ T helper cells. A unique feature of the antigen-presenting cell (APC) function of B cells is that these cells express a high affinity receptor for antigen in the form of the surface immunoglobulin (sIg) component of the B-cell antigen receptor (BCR). Earlier studies suggest that, in addition to its role in antigen delivery, the BCR transduces signals that increase the loading of antigenic peptides onto MHC class II molecules in a post-Golgi compartment(s) termed the class II-peptide-loading compartment (II-PLC). The long range goal of this proposal is to further characterize the BCR-mediated antigen pathway in B cells, to extend the analyses of the receptors and factors which influence this pathway and to define the subcellular and molecular targets and mechanisms of such regulation.
The specific aims are: (1) to characterize the BCR-mediated antigen processing pathway and the components of the BCR required for proper trafficking of internalized antigens in these cells, (2) to survey heterologous cell surface receptors on B cells for their ability to modulate the efficiencies with which specific and nonspecific antigens are loaded onto MHC class II molecules, and (3) to define the steps in the trafficking pathway that are targeted by incoming regulatory signals from these cell surface receptors. The results of this will facilitate the development of new therapeutic strategies for vaccine development, and may lead to the development of novel immunosuppressive agents that specifically interfere with the APC function of B cells.
