Bacterial lipopolysaccharide (LPS) is one of a number of cell wall constituents of microbial origin which are polyclonal B cell activators (PBA's) and/or immunomodulatory agents. LPS is also known to interact with many other cellular and humoral host defense systems with pathological consequences to the host. The objective of the proposed research is to further our understanding of the nature of the interaction of immunomodulators with non-Ig receptors on B cells. Using LPS as the prototype ligand, we will examine the binding of LPS to target cells using immunofluorescent and radiobinding techniques. We will characterize the specific and non-specific binding, the membrane determinants of LPS-binding B cells, and the genetic control of LPS binding sites to confirm initial observations that specific LPS binding is primarily a characteristic of B cells, and that it occurs in responder and nonresponder strains of mice. The nature of LPS binding to amphibian lymphocytes will be explored using similar techniques to develop some perspective on the biological significance of mitogen receptors in the evolution and expression of humoral immunity. We will examine the biochemical control of LPS capping on B cells and compare the capping of this ligand to capping of other surface membrane components. Using a variety of extraction and separation procedures, we will attempt to identify the membrane component which is responsible for specific binding of LPS to murine lymphocytes.