Gamma globulin in the body is subject to continuous synthesis and breakdown. Synthesis is taking place in the plasma cells of the reticuloendothelial system (1--4). It is possible that catabolism takes place partly by leakage into the gastrointestinal tract and subsequent digestion by the intestinal proteolyfic enzymes (5) and partly in the liver (6). Several things are known about the regulation of the synthesis: for example intensive immunization will cause a rise in serum gamma globulin concentration by way of increased production (7)1 whereas adrenocortical hormones (81 9), various toxic agents I and pathological processes in the reticuloendothelial system may inhibit the production and lower the serum concentration of gamma globulin. But almost nothing is known about the regulation of the breakdown of gamma globulin.On the basis of exponential decline of gamma globulin infused into the blood stream of children suffering from agammaglobulinemia, Gitlin (10) concluded that the breakdown follows a first order rate process. In an attempt to elucidate the problem of the regulation of gamma globulin turnover, we have studied the turnover in rabbits with two widely different serum gamma globulin concentrations. The turnover was determined by means of xalI-labeled gamma globulin, first on normal level of serum gamma globulin and then, in the same rabbits, 4 to 8 weeks later, during hyperlmmunization by which the serum concentration was raised from 4 to 10 times above normal values.
MethodsMater/a/.--The study was carded out on seven rabbits of the Danish country race, bred in the State Serum Institute, weight 3 to 4 kg. The rabbits, which were 30 months old, had during the previous 24 months been hyperimmunized in five periods by intravenous injection of the same polyvalent pneumococcic vaccine as was used in the present study. They were apparently healthy, and the weight remained constant throughout the study.Gamma globulin was isolated from serum of normal rabbits of the same race by means of colnmn chromatography on diethyiaminoethyl (DEAE) cellulose 1 (11). Serum was dialyzed
The administration of adrenocorticotrophic hormone and of cortisone was found to result in a reduction in the concentration of antipneumococcal antibody in the circulation of rabbits. This reduction occurred both when the hormones were administered at the beginning of immunization and after immunization was well advanced. Marked atrophic changes in lymphoid tissue and a diminution in the number of various types of mononuclear cells followed upon the hormone administration. The possible bearing of these observations on theories concerning the sites of antibody production is discussed.
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