Monoclonal antibodies reveal the structural basis of antibody diversity

This chapter describes how the analysis of closely related families of monoclonal antibodies has provided new insights into the structural basis of antigen binding and the molecular mechanism responsible for antibody diversity. While the ability to sample the repertoire of antibodies through the analysis of monoclonal antibodies can provide important insights, some questions are hard to answer with this approach. The chapter discusses the instability of immunoglobulin genes in cultured myeloma and hybridoma cells. The specificity of the interactions of monoclonal antibodies to the idiotype and monoclonal antibodies and myeloma proteins of known sequence illustrates both the benefits and complexities of trying to use reagents to identify chemical relatedness. Monoclonal antibodies that no longer react with one or a few of those anti-idiotypic monoclonals are presumptive variants. The large amount of paraprotein in the serum of patients or animals with the malignancy is a monoclonal antibody that is produced by a transformed antibody-forming cell growing in an uncontrolled fashion.