IMMUNE RESPONSES IN VITRO VI. GENETIC CONTROL OF THE IN VIVO-IN VITRO DISCREPANCIES IN 19S ANTIBODY SYNTHESIS*

Contact with an antigenic substance results in a complex sequence of cellular and molecular events, the consequence of which is the acquisition of specifically sensitized lymphoid cells. These sensitized cells can synthesize and secrete antibody or react with the antigen via cell-mediated-type reactions. Despite the complexity of immuneassociated events, the orderly process and predictable nature of many biochemical parameters involved indicate that the response is efficiently regulated. Thus the controlling mechanisms most likely are also complex, and it is probable that the majority have yet to be described. One experimental means of investigating biological control mechanisms is the use of genetically defined "mutant" animals. Such mutants possessing immunologically associated genetic differences have already played important roles in understanding the intricacies of the immune response. Guinea pigs which are either responders or nonresponders to synthetic antigens have facilitated the analysis of antigen recognition (1 and references therein). Rabbits have been instrumental in determining the cell source of genetic information for the protein chains of immunoglobulins via allotypic markers (2, 3). Different mouse strains have been used to study the genetic control of the magnitude of the antibody response (1 and references therein, 4-9), the genetic analysis of differential responses to determinants on the same immunogen (10-12), and the genetic mapping of immune response genes (1 and references therein). Even though the variety of antigens to which the response is genetically influenced in mice is rapidly being enlarged, the immunological cell type in which the genetic markers are expressed is just beginning to be clearly defined (12-15). Moreover, mutations have yet to be instrumental in defining cell functions or immunological control mechanisms.