Monoclonal Antibodies by Somatic Cell Fusion

Abstract

Immunoglobulins or antibody molecules are synthesized by B-lymphocytes in response to a spectrum of biological macromolecules. Antibodies are bifunctional molecules that bind specifically to antigenic determinants on macromolecules and eliminate foreign substances through recruitment of effector mechanisms. The core structure of an antibody molecule comprises two identical, covalently-linked heavy chains that, in most instances, are covalently-linked to two identical light chains. Two distinct areas of the core structure, designated variable and constant regions, mediate the antigen binding and effector functions. The heavy and light chain variable region domains form the antigen binding site and the heavy chain constant region contains the recognition sites for a variety of effector systems. Due to the functional assembly and expression of single heavy and light chain alleles, each B cell expresses a homogenous population of antibody molecules of a single antigenic specificity. The ability to immortalize individual B-lymphocytes that produce monoclonal antibodies of a particular antigenic specificity is the basis of the somatic cell fusion or hybridoma technology (Köhler and Milstein, 1975. Monoclonal antibodies are standard tools and reagents in numerous scientific disciplines and their availability has expanded applications in diagnostics and therapeutics. The generation of rodent monoclonal antibodies by the hybridoma technology or somatic cell fusion has been very successful. This technology has resulted in the generation of thousands of monoclonal antibodies creating groups of antibodies with precisely defined antigenic specificities. This article presents an overview of monoclonal antibody production by somatic cell fusion using the mouse as the prototype animal model. Discussions of myeloma fusion partners, antigen choice and preparation, …