Abstract
In a search for possible genetic factors which may influence the immune response to the streptococcal carbohydrates, over 100 rabbits have been immunized with streptococcal vaccines, and representative examples of high and low response pairs mated. The concentration of precipitins to the group—specific carbohydrates has been measured in the antisera following primary intravenous immunization with heat-killed streptococcal vaccines, Group A, Group A-variant, and Group C. For the majority of rabbits, the concentration of precipitins varied between 1 and 10 mg/ml of antiserum; while in the minority, it was between 11 and 32 mg/ml. The offspring of rabbits with high antibody levels had a significantly higher concentration of antibody than was seen in the offspring of rabbits of low response parents. Such data suggest that the magnitude of the immune response to these carbohydrate antigens is under some form of genetic control. Not uncommonly in rabbits with hyper-γ-globulinemia following primary immunization, the group-specific precipitins are the predominant component of the γ-globulin. An unusual feature of such components is that they are electrophoretically monodisperse, and possess individual antigenic specificity. In this respect they resemble the myeloma proteins. When a response of this sort is not seen after primary immunization, it may occur after secondary immunization. Therefore, prior exposure to the same or closely related antigen may also have an influence on the occurrence of high concentrations of such uniform antibodies.
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- ALLLEN J. C., KUNKEL H. G., KABAT E. A. STUDIES ON HUMAN ANTIBODIES. II. DISTRIBUTION OF GENETIC FACTORS. J Exp Med. 1964 Mar 1;119:453–465. doi: 10.1084/jem.119.3.453. [DOI] [PMC free article] [PubMed] [Google Scholar]
- ASKONAS B. A., HUMPHREY J. H. Formation of antibody by isolated perfused lungs of immunized rabbits: the use of [14C]amino acids to study the dynamics of antibody secretion. Biochem J. 1958 Oct;70(2):212–222. doi: 10.1042/bj0700212. [DOI] [PMC free article] [PubMed] [Google Scholar]
- ASKONAS B. A., HUMPHREY J. H. Formation of specific antibodies and gamma-globulin in vitro; a study of the synthetic ability of various tissues from rabbits immunized by different methods. Biochem J. 1958 Feb;68(2):252–261. doi: 10.1042/bj0680252. [DOI] [PMC free article] [PubMed] [Google Scholar]
- AXELSSON U., HALLEN J. FAMILIAL OCCURRENCE OF PATHOLOGICAL SERUM-PROTEINS OF DIFFERENT GAMMA-GLOBULIN GROUPS. Lancet. 1965 Aug 21;2(7408):369–370. doi: 10.1016/s0140-6736(65)90344-2. [DOI] [PubMed] [Google Scholar]
- BLEIWEIS A. S., KARAKAWA W. W., KRAUSE R. M. IMPROVED TECHNIQUE FOR THE PREPARATION OF STREPTOCOCCAL CELL WALLS. J Bacteriol. 1964 Oct;88:1198–1200. doi: 10.1128/jb.88.4.1198-1200.1964. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Braun D. G., Krause R. M. The individual antigenic specificity of antibodies to streptococcal carbohydrates. J Exp Med. 1968 Nov 1;128(5):969–989. doi: 10.1084/jem.128.5.969. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Brenneman L., Singer S. J. The generation of antihapten antibodies with electrophoretically homogeneous L chains. Proc Natl Acad Sci U S A. 1968 May;60(1):258–264. doi: 10.1073/pnas.60.1.258. [DOI] [PMC free article] [PubMed] [Google Scholar]
- COHEN C., TISSOT R. G. BLOOD GROUPS IN THE RABBIT. TWO ADDITIONAL ISOANTIBODIES AND THE RED CELL CANTIGENS THEY IDENTIFY. J Immunol. 1965 Jul;95:148–155. [PubMed] [Google Scholar]
- Davie J. M., Osterland C. K., Miller E. J., Krause R. M. Immune cryoglobulins in rabbit streptococcal antiserum. J Immunol. 1968 Apr;100(4):814–820. [PubMed] [Google Scholar]
- EDELMAN G. M., KABAT E. A. STUDIES ON HUMAN ANTIBODIES. I. STARCH GEL ELECTROPHORESIS OF THE DISSOCIATED POLYPEPTIDE CHAINS. J Exp Med. 1964 Mar 1;119:443–452. doi: 10.1084/jem.119.3.443. [DOI] [PMC free article] [PubMed] [Google Scholar]
- FUDENBERG H., GERMAN J. L., 3rd, KUNKEL H. G. The occurrence of rheumatoid factor and other abnormalities in families of patients with agammaglobulinemia. Arthritis Rheum. 1962 Dec;5:565–588. doi: 10.1002/art.1780050605. [DOI] [PubMed] [Google Scholar]
- Fleischman J. B., Braun D. G., Krause R. M. Streptococcal group-specific antibodies: occurrence of a restricted population following secondary immunization. Proc Natl Acad Sci U S A. 1968 May;60(1):134–139. doi: 10.1073/pnas.60.1.134. [DOI] [PMC free article] [PubMed] [Google Scholar]
- GREY H. M., MANNIK M., KUNKEL H. G. INDIVIDUAL ANTIGENIC SPECIFICITY OF MYELOMA PROTEINS. CHARACTERISTICS AND LOCALIZATION TO SUBUNITS. J Exp Med. 1965 Apr 1;121:561–575. doi: 10.1084/jem.121.4.561. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gill T. J., 3rd Studies on synthetic polypeptide antigens. XIV. Variations in antibody production among rabbits of different inbred strains. J Immunol. 1965 Sep;95(3):542–545. [PubMed] [Google Scholar]
- HUMPHREY J. H., SULITZEANU B. D. The use of [14C] amino acids to study sites and rates of antibody synthesis in living hyperimmune rabbits. Biochem J. 1958 Jan;68(1):146–161. doi: 10.1042/bj0680146. [DOI] [PMC free article] [PubMed] [Google Scholar]
- KARAKAWA W. W., OSTERLAND C. K., KRAUSE R. DETECTION OF STREPTOCOCCAL GROUP-SPECIFIC ANTIBODIES IN HUMAN SERA. J Exp Med. 1965 Aug 1;122:195–205. doi: 10.1084/jem.122.2.195. [DOI] [PMC free article] [PubMed] [Google Scholar]
- KRAUSE R. M., McCARTY M. Studies on the chemical structure of the streptococcal cell wall. II. The composition of group C cell walls and chemical basis for serologic specificity of the carbohydrate moiety. J Exp Med. 1962 Jan 1;115:49–62. doi: 10.1084/jem.115.1.49. [DOI] [PMC free article] [PubMed] [Google Scholar]
- KRITZMAN J., KUNKEL H. G., MCCARTHY J., MELLORS R. C. Studies of a Waldenstrom-type macroglobulin with rheumatoid factor properties. J Lab Clin Med. 1961 Jun;57:905–917. [PubMed] [Google Scholar]
- Karakawa W. W., Braun D. G., Lackland H., Krause R. M. Immunochemical studies on the cross-reactivity between streptococcal and staphylococcal mucopeptide. J Exp Med. 1968 Aug 1;128(2):325–340. doi: 10.1084/jem.128.2.325. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kunkel H. G., Mannik M., Williams R. C. Individual Antigenic Specificity of Isolated Antibodies. Science. 1963 Jun 14;140(3572):1218–1219. doi: 10.1126/science.140.3572.1218. [DOI] [PubMed] [Google Scholar]
- LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
- Lancefield R. C. A SEROLOGICAL DIFFERENTIATION OF HUMAN AND OTHER GROUPS OF HEMOLYTIC STREPTOCOCCI. J Exp Med. 1933 Mar 31;57(4):571–595. doi: 10.1084/jem.57.4.571. [DOI] [PMC free article] [PubMed] [Google Scholar]
- MCCARTY M. The lysis of group A hemolytic streptococci by extracellular enzymes of Streptomyces albus. II. Nature of the cellular substrate attacked by the lytic enzymes. J Exp Med. 1952 Dec;96(6):569–580. doi: 10.1084/jem.96.6.569. [DOI] [PMC free article] [PubMed] [Google Scholar]
- McCARTY M. The occurrence of polyglycerophosphate as an antigenic component of various gram-positive bacterial species. J Exp Med. 1959 Apr 1;109(4):361–378. doi: 10.1084/jem.109.4.361. [DOI] [PMC free article] [PubMed] [Google Scholar]
- McDevitt H. O., Sela M. Genetic control of the antibody response. I. Demonstration of determinant-specific differences in response to synthetic polypeptide antigens in two strains of inbred mice. J Exp Med. 1965 Sep 1;122(3):517–531. doi: 10.1084/jem.122.3.517. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Miller E. J., Osterland C. K., Davie J. M., Krause R. M. Electrophoretic analysis of polypeptide chains isolated from antibodies in the serum of immunized rabbits. J Immunol. 1967 Apr;98(4):710–715. [PubMed] [Google Scholar]
- Osterland C. K., Miller E. J., Karakawa W. W., Krause R. M. Characteristics of streptococcal group-specific antibody isolated from hyperimmune rabbits. J Exp Med. 1966 Apr 1;123(4):599–614. doi: 10.1084/jem.123.4.599. [DOI] [PMC free article] [PubMed] [Google Scholar]
- PORTER D. D., DIXON F. J., LARSEN A. E. THE DEVELOPMENT OF A MYELOMA-LIKE CONDITION IN MINK WITH ALEUTIAN DISEASE. Blood. 1965 May;25:736–742. [PubMed] [Google Scholar]
- Pappenheimer A. M., Jr, Reed W. P., Brown R. Quantitative studies of the specificity of anti-pneumococcal polysaccharide antibodies, types 3 and 8. 3. Binding of a labeled oligosaccharide derived from S8 by anti-S8 antibodies. J Immunol. 1968 Jun;100(6):1237–1244. [PubMed] [Google Scholar]
- Pinchuck P., Maurer P. H. Antigenicity of polypeptides (poly alpha amino acids). XVI. Genetic control of immunogenicity of synthetic polypeptides in mice. J Exp Med. 1965 Oct 1;122(4):673–679. doi: 10.1084/jem.122.4.673. [DOI] [PMC free article] [PubMed] [Google Scholar]
- SANG J. H., SOBEY W. R. The genetic control of response to antigenic stimuli. J Immunol. 1954 Jan;72(1):52–65. [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]
- Simonian S. J., Gill T. J., 3rd, Gershoff S. N. Studies on synthetic polypeptide antigens. XX. Genetic control of the antibody response in the rat to structurally different synthetic polypeptide antigens. J Immunol. 1968 Oct;101(4):730–742. [PubMed] [Google Scholar]
- Williams R. C., Jr, Erickson J. L., Polesky H. F., Swaim W. R. Studies of monoclonal immunoglobulins (M-components) in various kindreds. Ann Intern Med. 1967 Aug;67(2):309–327. doi: 10.7326/0003-4819-67-2-309. [DOI] [PubMed] [Google Scholar]
- Yount W. J., Dorner M. M., Kunkel H. G., Kabat E. A. Studies on human antibodies. VI. Selective variations in subgroup composition and genetic markers. J Exp Med. 1968 Mar 1;127(3):633–646. doi: 10.1084/jem.127.3.633. [DOI] [PMC free article] [PubMed] [Google Scholar]