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 which have been examined. The goal of these studies is: (a) to examine the role of calcium- calmodulin dependent protein kinases and phosphatases that are induced upon activation of B cells in regulating the transcription of immunoglobulin genes, and (b) to examine the ability of a variety of differentiation of B cells) to modulate the function and the nuclear transcription of immunoglobulin heavy and light chain, cytokines (transforming growth factor), bacterial mitogens, pharmacologic agents and immunosuppressive drugs. The mechanism of action of these agents will be explored by examining their effects on the rate of transcription of immunoglobulin genes. Particular emphasis will be placed in detecting similarities, differences, synergism or antagonism in their effects.
