We are interested in understanding the molecular control of antibody responses by B cells. We previously identified a novel costimulatory molecule, B7h, expressed on B cells and other antigen-presenting cells that is the sole in vivo ligand for the ICOS costimulatory receptor expressed on activated T cells. B7h is highly regulated and appears to be a critical control point on B cells for controlling the magnitude of antibody responses. We have identified two potent mechanisms, ectodomain shedding and transcriptional regulation, that severely limit B7h expression on activated B cells. We are currently studying how these molecular mechanisms are regulated and control antibody responses using both in vitro tissue culture assays and transgenic/knockout mouse models.