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Intravenously administered 7S antibody is more effective than 19S antibody in inhibiting the formation of antibody to bacteriophage X174. Since considerable amounts of 7S antibody are needed for inhibition, serum antibody formation may act as a "feedback" mechanism to prevent hyperimmunization.

Quantitative studies of antibody formation in experimental animals have been facilitated by the use of labeled proteins (1, 2). After equilibration following intravenous injection, labeled antigen is eliminated from the circulation in two exponential phases: the first and slower rate is due to non-immune catabolism; the second and rapid decline is caused by the production and release into the circulation of specific antibody (3, 4).In this study, guinea pigs have been injected with relatively minute amounts of a small bacteriophage, 4~X 174, which has been traced in the circulation utilizing the plaque-forming capacity of the virus. With this method it has been possible to detect an immune elimination as early as 24 hours after injection. The early detection of antibody was facilitated by the small amounts of antigen employed. It has also been shown that there is a close resemblance between the kinetics of the primary and secondary antibody response to this bacteriophage. Materials and MethodsPhage.--Str~J.us of ~bX 174 and T2 were kindly supplied to us by Dr. E. Lennox. ~bX was grown in Escherickia coli strain C in glycerol-easamino acid medium (5). The lysed culture was centrifuged at low speed to remove cell debris. Purification was then accomplished by precipitation with ammonium sulfate, passage through a DEAE cellulose anion exchange column, and elution with 0.1 M ammonium acetate (6). This purified stock containing 10 n plaque-forming particles per ml was kept at 4°C in ammonium acetate buffer pH 7.4 conraining 0.01 per cent gelatin. Dilutions of this stock were used for almost all the immunization experiments.

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Following the injection of any one of various antigens into humans (1, 2) and rabbits (3-5), rapidly sedimenting antibody molecules (19S) first appear in the circulation, and later are replaced by molecules of 7S sedimentation constant. Similar results were obtained after injection of bacteriophage q~X 174 into guinea pigs (6), newborn humans (7), sheep embryos (8), and several non-mammalian vertebrates (9), indicating the general occurrence of this sequence in the immune response.Earlier studies of antiMX formation in guinea pigs indicated certain similarities between the kinetics of primary 19S and secondary 7S antibody formations (6). The purpose of this study was to investigate the decline of 19S antibody formation, the primary 7S antibody response, and the relationship between the two responses. The results indicate that primary 7S antibody formation lasts for months and leads to preparation for a secondary 7S antibody response (immunological memory). In contrast, 19S antibody formation is relatively short-lived and in these studies did not lead to persisting immunological memory. It has also been shown that antigen can regulate the relative rate of antibody formation and the duration of rapidly sedimenting antibody synthesis, suggesting that the amount of antigen in immunologically competent cells may serve as a major control mechanism for several immunological functions. Materials and MethodsPhage.--Two preparations of bacteriophage ~X 174 were used. The first, grown in E. coli strain C on glyeerol--casamino acid media (10) and purified by the method previously described (6), contained 4.5 X 1011 plaque-forming particles/ml. A second stock of ~bX, kindly * Aided by