Chapter 7 - Plasma Cells Produce Antibody of a Single Specificity

Abstract

A tenet of F. Macfarlane Burnet's clonal selection theory is that a potential antibody-forming cell is genetically preprogrammed to synthesize antibodies of a single specificity. Gus Nossal, one of Burnet's colleagues, proposed that the theory could be disproved if a single cell produced antibodies of different specificities. Nossal, along with Joshua Lederberg, designed an experiment using a technique allowing them to detect the specificity of antibodies produced by individual antibody-producing cells. This microdrop technique, used with several different antigens, consistently demonstrated that virtually all cells tested produced antibodies of a single specificity; this led to the concept of one cell:one antibody. Support for this conclusion came from other studies, including immunofluorescent observations of antibody-forming cells and identification of the cell surface receptors on B lymphocytes. In the clinic, patients with multiple myeloma, a disease characterized by the appearance in serum of a large amount of homogeneous immunoglobulin, possess malignantly transformed cells, all of which arise from a single precursor and synthesize a single immunoglobulin molecule. Production of antibody of a single specificity by plasma cells allowed development of monoclonal antibodies that have greatly enhanced the therapeutic and laboratory choices available to investigators.