Abstract
The nature of the antibodies produced by the rabbit during the primary and secondary responses to T2 phage, proteins, and the O and H antigens of Salmonella typhosa has been determined. Immune sera have been fractionated by zone electrophoresis, sucrose density ultracentrifugation, and anion exchange chromatography. The resulting fractions have been assayed by phage neutralization or hemagglutination (antisera to proteins) or bacterial agglutination. In confirmation and extension of earlier work from this laboratory, the primary response to these antigens, with the exception of the O antigen of the Salmonella, included the early synthesis of 19S, γ-1 globulin antibody, and the later synthesis of 7S, γ-2 globulin antibody. The primary response to the O antigen consisted of the synthesis of only a macroglobulin agglutinin. The secondary response to the proteins, including the H antigen of the Salmonella, comprised the early synthesis of large amounts of the 7S γ-2 globulin antibody to the same level attained during the primary response. The secondary response to the phage consisted in the synthesis of 7S, γ-2 globulin antibody alone. Treatment of the macroglobulin phage-neutralizing antibody with mercaptoethanol resulted in complete loss of its neutralizing activity. A working hypothesis to explain these observations was presented. A salient feature of this hypothesis was the suggestion that different cells synthesized the two distinct molecular forms of antibody. The significance of the sequential synthesis of the two forms of antibody is not known. It was proposed that the system for synthesis of macroglobulin antibody is an auxiliary system for antibody synthesis, perhaps the first to develop phylogenetically and ontogenetically. It is felt that the present observations indicate a clear-cut qualitative distinction between the primary and secondary responses to immunization whereby these responses might be identified in various experimental situations. It is also felt that these findings with the primary and secondary responses to various antigens in the rabbit may be of widespread occurrence in nature among a variety of species.
Full Text
The Full Text of this article is available as a PDF (1.1 MB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- BENEDICT A. A., BROWN R. J., AYENGAR R. Physical properties of antibody to bovine serum albumin as demonstrated by hemagglutination. J Exp Med. 1962 Jan 1;115:195–208. doi: 10.1084/jem.115.1.195. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bauer D. C., Stavitsky A. B. ON THE DIFFERENT MOLECULAR FORMS OF ANTIBODY SYNTHESIZED BY RABBITS DURING THE EARLY RESPONSE TO A SINGLE INJECTION OF PROTEIN AND CELLULAR ANTIGENS. Proc Natl Acad Sci U S A. 1961 Oct;47(10):1667–1680. doi: 10.1073/pnas.47.10.1667. [DOI] [PMC free article] [PubMed] [Google Scholar]
- CANN J. R., CLARK E. W. On the kinetics of neutralization of bacteriophage T2 by specific antiserum. J Immunol. 1954 Jun;72(6):463–477. [PubMed] [Google Scholar]
- DEUTSCH H. F., MORTON J. I. Dissociation of human serum macroglobulins. Science. 1957 Mar 29;125(3248):600–601. doi: 10.1126/science.125.3248.600. [DOI] [PubMed] [Google Scholar]
- EDELMAN G. M., KUNKEL H. G., FRANKLIN E. C. Interaction of the rheumatoid factor with antigen-antibody complexes and aggregated gamma globulin. J Exp Med. 1958 Jul 1;108(1):105–120. doi: 10.1084/jem.108.1.105. [DOI] [PMC free article] [PubMed] [Google Scholar]
- FRASER D., JERREL E. A. The amino acid composition of T3 bacteriophage. J Biol Chem. 1953 Nov;205(1):291–295. [PubMed] [Google Scholar]
- FUDENBERG H. H., KUNKEL H. G. Physical properties of the red cell agglutinins in acquired hemolytic anemia. J Exp Med. 1957 Nov 1;106(5):689–702. doi: 10.1084/jem.106.5.689. [DOI] [PMC free article] [PubMed] [Google Scholar]
- HEIMLICH E. M., VANNIER W. E., CAMPBELL D. H. Sedimentation studies of skin-sensitizing antibody. J Allergy. 1960 Jul-Aug;31:364–369. doi: 10.1016/0021-8707(60)90072-1. [DOI] [PubMed] [Google Scholar]
- JERNE N. K. Bacteriophage inactivation by antiphage serum diluted in distilled water. Nature. 1952 Jan 19;169(4290):117–118. doi: 10.1038/169117b0. [DOI] [PubMed] [Google Scholar]
- LOSPALLUTO J., MILLER W., Jr, DORWARD B., FINK C. W. The formation of macroglobulin antibodies. I. Studies on adult humans. J Clin Invest. 1962 Jul;41:1415–1421. doi: 10.1172/JCI104596. [DOI] [PMC free article] [PubMed] [Google Scholar]
- MULLER-EBERHARD H. J. A new supporting medium for preparative electrophoresis. Scand J Clin Lab Invest. 1960;12:33–37. [PubMed] [Google Scholar]
- NISONOFF A., MARKUS G., WISSLER F. C. Separation of univalent fragments of rabbit antibody by reduction of a single, labile disulphide bond. Nature. 1961 Jan 28;189:293–295. doi: 10.1038/189293a0. [DOI] [PubMed] [Google Scholar]
- NOSSAL G. J., MAKELA O., ENGEL M. L., FEFER A. Cellular proliferation in immunity. Stanford Med Bull. 1962 Feb;20:32–36. [PubMed] [Google Scholar]
- PETERSON E. A., WYCKOFF M. M., SOBER H. A. Gradient chromatography of human serum proteins and its application to the examination of "albumin" and "globulin" obtained by ammonium sulfate fractionation. Arch Biochem Biophys. 1961 May;93:428–434. doi: 10.1016/0003-9861(61)90289-2. [DOI] [PubMed] [Google Scholar]
- SCHEIDEGGER J. J. Une micro-méthode de l'immuno-electrophorèse. Int Arch Allergy Appl Immunol. 1955;7(2):103–110. [PubMed] [Google Scholar]
- SOBER H. A., PETERSON E. A. Protein chromatography on ion exchange cellulose. Fed Proc. 1958 Dec;17(4):1116–1126. [PubMed] [Google Scholar]
- STAVITSKY A. B., ARQUILLA E. R. Studies of proteins and antibodies by specific hemagglutination and hemolysis of proteinconjugated erythrocytes. Int Arch Allergy Appl Immunol. 1958;13(1-2):1–38. doi: 10.1159/000228473. [DOI] [PubMed] [Google Scholar]
- STAVITSKY A. B. Micromethods for the study of proteins and antibodies. I. Procedure and general applications of hemagglutination and hemagglutination-inhibition reactions with tannic acid and protein-treated red blood cells. J Immunol. 1954 May;72(5):360–367. [PubMed] [Google Scholar]
- STELOS P., TALMAGE D. W. The separation by starch electrophoresis of two antibodies in sheep red cells differing in hemolytic efficiency. J Infect Dis. 1957 Mar-Apr;100(2):126–135. doi: 10.1093/infdis/100.2.126. [DOI] [PubMed] [Google Scholar]
- UHR J. W., DANCIS J., FRANKLIN E. C., FINKELSTEIN M. S., LEWIS E. W. The antibody response to bacteriophage phi-X 174 in newborn premature infants. J Clin Invest. 1962 Jul;41:1509–1513. doi: 10.1172/JCI104606. [DOI] [PMC free article] [PubMed] [Google Scholar]
- UHR J. W., FINKELSTEIN S., FRANKLIN E. C. Antibody response to bacteriophage phi-X-174 in non-mammalian vertebrates. Proc Soc Exp Biol Med. 1962 Oct;111:13–15. doi: 10.3181/00379727-111-27691. [DOI] [PubMed] [Google Scholar]
- WALLENIUS G., TRAUTMAN R., KUNKEL H. G., FRANKLIN E. C. Ultracentrifugal studies of major non-lipide electrophoretic components of normal human serum. J Biol Chem. 1957 Mar;225(1):253–267. [PubMed] [Google Scholar]