ABSTRACT
In 1948, Astrid Elsa Fagraeus established the role of the plasma cell in antibody formation. The fluorescence antibody technique developed by Albert Coons was a major breakthrough for the identification of antigen in tissues and subsequently demonstrated antibody synthesis by individual cells. While attempting to immunize chickens in which the bursa of Fabricius had been removed, Bruce Glick et al. noted that antibody production did not take place. This was the first evidence of bursa-dependent antibody formation. Robert A. Good immediately realized the significance of this finding for immunodeficiencies of childhood. He and his associates in Minneapolis and J.F.A.P. Miller in England went on to show the role of the thymus in the immune response, and various investigators began to search for bursa equivalence in man and other animals. Thus, the immune system of many species was found to
have distinct bursa-dependent, antibody-synthesizing, and thymus-dependent cell-mediated limbs. In 1959, James Gowans proved that lymphocytes actually recirculate. In 1966, Tzvee Nicholas Harris et al. demonstrated clearly that lymphocytes could form antibodies. In 1966 and 1967, Claman et al., David et al., and Mitchison et al. showed that T and B lymphocytes cooperate with one another in the production of an immune response. Various phenomena such as the switch from forming one class of immunoglobulin to another by B cells were demonstrated to be dependent upon a signal from T cells activating B cells to change from IgM to IgG or IgA production. B cells stimulated by antigen in which no T cell signal was given continued to produce IgM antibody. Such antigens were referred to as thymus-independent antigens, and others requiring T cell participation as thymus-dependent antigens. Mitchison et al. described a subset of T lymphocytes demonstrating helper activity, i.e., helper T cells. In 1971, Gershon and Condo described suppressor T cells. Suppressor T cells have been the subject of much investigation but have eluded confirmation by the techniques of molecular biology. Baruj Benacerraf et al. demonstrated the significant role played by gene products of the major histocompatibility complex in the specificity and regulation of T cell-dependent immune response. Jerne described the network theory of immunity in which antibodies formed against idiotypic specificities of antibody molecules followed by the formation of antiidiotypic
antibodies constitutes a significant additional immunoregulatory process for immune system function. This postulate has been proved valid by numerous investigators. Tonegawa et al. and Leder et al. identified and cloned the genes that code for variable and constant diversity in antibody-combining sites. In 1975, George Kohler and Cesar Milstein successfully produced monoclonal antibodies by hybridizing mutant myeloma cells with antibody-producing B cells (hybridoma technique). The B cells conferred the antibody-producing capacity while the myeloma cells provided the capability for endless reproduction. Monoclonal antibodies are the valuable homogeneous products of hybridomas that have widespread application in diagnostic laboratory medicine.
