The studies described in this proposal are designed to further our understanding of the structure and function of antibody molecules, the relationship of immune complexes to human disease and the characterization of the major protein constituents of amyloid. The experiments dealing with antibody molecules and immunoglobulin variants produced by normal individuals as well as those with multiple myeloma and related plasma cell neoplasms are expected to shed insight into the genetic control of immunoglobulin structure and synthesis, to define the antibody combining sites and the expression of novel immunoglubulin genes. We wish to determine the factors involved in the production of rheumatoid factor cryoglobulins which result in an immune complex type of nephritis and vasculitis. Finally, we are attempting to classify from a clinical, immunohistologic and biochemical point of view a heterogeneous group of diseases characterized by the deposition of amyloid fibrils. Our approach is based on the theory that all types of amyloidosis occur in individuals who are genetically or otherwise defective in processing a soluble precursor which is a normal serum component.