Jane R. Parnes, MD, Stanford University

The Parnes laboratory is interested in CD72, which is a B lymphocyte surface protein expressed from early stages of B cell development through to the mature B cell stage, but its expression is turned off as B cells differentiate into plasma cells. To elucidate the function of CD72 they have used gene targeting to generate homozygous mutant mice that totally lack CD72 expression. The B cells in these mice are hyper-responsive to stimulation through the B cell receptor. These data indicate that CD72 plays a negative regulatory role on B cell responsiveness. They postulate that CD72 is involved in setting the threshold for B cell responsiveness and that it therefore plays an important role in B cell repertoire selection. Their current studies are examining how CD72 regulates the balance between B cell tolerance and autoimmunity in several model systems. They have evidence that the CD72-deficient mice are more susceptible to the induced autoimmune disease experimental allergic encephalomyelitis, a mouse model of multiple sclerosis. They are studying the mechanisms responsible for the increased severity of disease in CD72-deficient mice. Current studies are aimed at further characterizing the autoantibodies produced, determining the regulatory changes responsible for their production, as well as their pathogenicity. They are additionally studying the mechanisms by which CD72-deficiency leads to a partial abrogation of B cell anergic tolerance in mice in which all B cells express a transgenic B cell receptor specific for hen-egg lysozyme (HEL) and in which the antigen HEL is expressed in the serum. Finally, the lab is examining the biochemistry of signaling through CD72 to determine the molecular mechanisms by which CD72 regulates B cell responsiveness.