Reduction of pathogenic autoantibodies is the main objective in the therapy of immune mediated renal diseases. Although rates of immunoglobulin synthesis can be regulated at multiple levels, most attention has been focused on transcription, as this seems to be the limiting step in most situations that have been examined. The goal of these studies is to examine the ability of a variety of agents (known to regulate the activation, proliferation and differentiation of B cells) to modulate the nuclear transcription of immunoglobulin heavy and light chain genes. These agents include antibodies to surface immunoglobulin, cytokines (interleukins, interferon, transforming growth factor), bacterial mitogens, pharmacologic agents (ionomycin, phorbol esters, prostaglandins) and immunosuppressive drugs (glucocorticoids, cyclosporin, cyclophosphamide). The mechanism of action of these agents will be explored by examining their effects on the production of transcription factors necessary for immunoglobulin gene transcription. Particular emphasis will be placed in detecting similarities, differences, synergism or antagonism in their effects.
