This research will utilize a multidisciplinary approach to study modulation of immunoglobulin synthesis and the immune response to Group A streptococci. The studies, though broad in scope, will be kept relatively simple by utilizing, for the most part, a single antigen - or derivatives thereof, from Group A streptococcal carbohydrate (SACHO) - and 2 animal test systems (chicken and rat). Two approaches are being employed, namely; (1) The modulation of immunoglobulin ontogeny by bursectomy, thymectomy, splenectomy, pinealectomy and anti-immunoglobulin treatment at various times during embryongenesis and neonatal life; (2) Modulation of the immune response via surgical manipulation, gnotobiosis and cell transfer experiments. Both approaches place their emphasis on differentiation of the plasma cell line and ultimate responsiveness to Group A streptococcal carbohydrate. A broad spectrum of information directly related to the regulation and physiological functions of the various components of the immunological system will be forthcoming as a result of the basic experimental design. The studies have direct relevance to human physiology and pathology including sequelae to streptococcal infection, allergyk transplantation, hypergammaglobulinemia, hypogammaglobulinemia, agammaglobulinemia, sickle-cell anemia, cholecystitis, the bacterial carrier-state and the secretory immunological system.