B cells in germinal centers will undergo apoptosis unless they interact with a cognate T cell. This interaction is critical in rescuing specific B cells and shaping the serologic response to antigen. In systemic lupus, B cells secreting anti-DNA antibodies appear to proliferate in germinal centers and escape deletion by interaction with cognate T cells that recognized a Class II histocompatibility molecule with its associated peptide on the autoreactive B cell. We producing B cells to identify we propose to isolate peptides of immunoglobulin variable regions or the DNA binding proteins that may be recognized by T cells in germinal centers. Concurrently, as an integral part of this study we propose to isolate T cells that are activated by the Class II-peptide complex on anti-DNA producing B cells. These studies should help dissect at a molecular level the B cell processing and B and T cell interactions that permit the production of pathogenic anti-DNA antibodies in systemic lupus.
