Studies on globulin and antibody production in mice thymectomized at birth (original) (raw)

Abstract

Serum globulin levels and antibody against sheep red cells, Salmonella typhi (`O' and `H'), haemocyanin and pneumococcus type 3 capsular polysacharide (SSS III) were studied in C3H/Bi and C57BL×C3H/Bi F1 hybrid mice thymectomized within 18 hours of birth. Thymectomized mice tend to recover more slowly than intact mice from the physiological hypo-γ-globulinaemia present 3–4 weeks after birth, but the majority of mice that survived beyond 6 weeks had serum globulin levels comparable to those in intact animals. Increased γ1A-globulin levels were observed in some thymectomized mice which survived for 7 weeks or more and the immuno-electrophoretic patterns sometimes resembled those seen in mice with γ1A myelomas. Macroglobulin (γ1M) was detected in the sera of thymectomized mice which contained normal amounts of γ-globulin.

Total serum protein levels of groups of thymectomized and intact mice were not significantly different. The turnover rate of plasma albumin was also closely similar in both groups, but that of γ-globulin was accelerated in most of the thymectomized mice examined.

Antibodies against SSS III, sheep red cell agglutinins and typhoid `H' agglutinins behaved as 7S globulins, in contrast with sheep red cell haemolysins which belonged to the 19S group.

Antibody levels following primary stimulation with sheep red cells and Salmonella antigens were usually, but not always, much lower in thymectomized mice than in intact control mice. However antibody levels against haemocyanin and SSS III were within the range of controls in more than half the thymectomized mice. Few thymectomized mice after stimulation with a mixture of three antigens failed to give a detectable antibody response to all the antigens, and some responded as well as did intact mice.

The significance of these findings is discussed in relation to current theories of the function of the thymus in the development of immune responses.

Many of the older thymectomized mice showed a characteristic wasting syndrome, but it is unlikely that a general failure of antibody response can account for this. Evidence for the presence of auto-antibodies against red cells or nuclear or cytoplasmic constituents was sought but was not found.

419

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. ASKONAS B. A. A study on globulin formation by plasma-cell neoplasm (5563) transplantable in mice. Biochem J. 1961 Apr;79:33–43. doi: 10.1042/bj0790033. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. AUERBACH R. Genetic control of thymus lymphoid differentiation. Proc Natl Acad Sci U S A. 1961 Aug;47:1175–1181. doi: 10.1073/pnas.47.8.1175. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. BERENBAUM M. C. Effect of cytotoxic agents on antibody production. Nature. 1960 Jan 16;185:167–168. doi: 10.1038/185167a0. [DOI] [PubMed] [Google Scholar]
  4. CHARLWOOD P. A. Applications of radioactively labeled marker proteins in density gradient ultracentrifugation. Anal Biochem. 1963 Mar;5:226–245. doi: 10.1016/0003-2697(63)90120-9. [DOI] [PubMed] [Google Scholar]
  5. EAST J., PARROT D. M. Operative techniques for newborn mice using anaesthesia by cooling. J Endocrinol. 1962 Apr;24:249–250. doi: 10.1677/joe.0.0240249. [DOI] [PubMed] [Google Scholar]
  6. EAST J., PARROTT D. M., CHESTERMAN F. C., POMERANCE A. THE APPEARANCE OF A HEPATOTROPHIC VIRUS IN MICE THYMECTOMIZED AT BIRTH. J Exp Med. 1963 Dec 1;118:1069–1082. doi: 10.1084/jem.118.6.1069. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. FAHEY J. L., HUMPHREY J. H. Antibodies with differing molecular sizes in mice. Immunology. 1962 Jan;5:104–109. [PMC free article] [PubMed] [Google Scholar]
  8. FAHEY J. L., HUMPHREY J. H. Effect of transplantable plasma-cell tumors on antibody response in mice. Immunology. 1962 Jan;5:110–115. [PMC free article] [PubMed] [Google Scholar]
  9. GEDIN H. I., PORATH J. Studies of zone electrophoresis in vertical columns. II. Zone electrophoresis of serum proteins. Biochim Biophys Acta. 1957 Oct;26(1):159–169. doi: 10.1016/0006-3002(57)90067-7. [DOI] [PubMed] [Google Scholar]
  10. HELYER B. J., HOWIE J. B. Spontaneous auto-immune disease in NZB/BL mice. Br J Haematol. 1963 Apr;9:119–131. doi: 10.1111/j.1365-2141.1963.tb05450.x. [DOI] [PubMed] [Google Scholar]
  11. Humphrey J. H., Fahey J. L. THE METABOLISM OF NORMAL PLASMA PROTEINS AND GAMMA-MYELOMA PROTEIN IN MICE BEARING PLASMA-CELL TUMORS. J Clin Invest. 1961 Sep;40(9):1696–1705. doi: 10.1172/JCI104392. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. JANKOVIC B. D., WAKSMAN B. H., ARNASON B. G. Role of the thymus in immune ractions in rats. I. The immunologic response to bovine serum albumin (antibody formation, Arthus reactivity, and delayed hypersensitivity) in rats thymectomized or splenectomized at various times after birth. J Exp Med. 1962 Aug 1;116:159–176. doi: 10.1084/jem.116.2.159. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. LEVEY R. H., TRAININ N., LAW L. W. EVIDENCE FOR FUNCTION OF THYMIC TISSUE IN DIFFUSION CHAMBERS IMPLANTED IN NEONATALLY THYMECTOMIZED MICE. PRELIMINARY REPORT. J Natl Cancer Inst. 1963 Aug;31:199–217. [PubMed] [Google Scholar]
  14. MARTINEZ C., KERSEY J., PAPERMASTER B. W., GOOD R. A. Skin homograft survival in thymectomized mice. Proc Soc Exp Biol Med. 1962 Jan;109:193–196. doi: 10.3181/00379727-109-27149. [DOI] [PubMed] [Google Scholar]
  15. MILLER J. F. Immunological function of the thymus. Lancet. 1961 Sep 30;2(7205):748–749. doi: 10.1016/s0140-6736(61)90693-6. [DOI] [PubMed] [Google Scholar]
  16. OSOBA D., MILLER J. F. EVIDENCE FOR A HUMORAL THYMUS FACTOR RESPONSIBLE FOR THE MATURATION OF IMMUNOLOGICAL FACULTY. Nature. 1963 Aug 17;199:653–654. doi: 10.1038/199653a0. [DOI] [PubMed] [Google Scholar]
  17. PARROTT D. M., EAST J. Role of the thymus in neonatal life. Nature. 1962 Jul 28;195:347–348. doi: 10.1038/195347a0. [DOI] [PubMed] [Google Scholar]
  18. PARROTT D. M. Strain variation in mortality and runt disease in mice thymectomized at birth. Transplant Bull. 1962 Apr;29:102–104. [PubMed] [Google Scholar]
  19. POTTER M., FAHEY J. L. Studies on eight transplantable plasma-cell neoplasms of mice. J Natl Cancer Inst. 1960 May;24:1153–1165. [PubMed] [Google Scholar]
  20. SCHEIDEGGER J. J. Une micro-méthode de l'immuno-electrophorèse. Int Arch Allergy Appl Immunol. 1955;7(2):103–110. [PubMed] [Google Scholar]
  21. STELOS P. Electrophoretic and ultracentrifugal studies on rabbit hemolysins. J Immunol. 1956 Dec;77(6):396–404. [PubMed] [Google Scholar]
  22. TOMBS M. P., SOUTER F., MACLAGAN N. F. The spectrophotometric determination of protein at 210 millimicrons. Biochem J. 1959 Sep;73:167–171. doi: 10.1042/bj0730167. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. WALDENSTROM J. Monoclonal and polyclonal gammopathies and the biological system of gamma globulins. Prog Allergy. 1962;6:320–348. [PubMed] [Google Scholar]