Skip to main content
NCBI home page
Immunology logoLink to Immunology
. 1966 Dec;11(6):571–588.

The coexistence of antibody with antigen during immunological paralysis to BSA

J H Day, R S Farr
PMCID: PMC1423813  PMID: 5954774

Abstract

Nine adult rabbits averaging 2.55 kg were each given 1.275 g bovine serum albumin (BSA Fraction V) 6 days weekly for a period of 66 days and rechallenged with 50 mg BSA or human serum albumin (HSA) 139 days after the last injection of BSA. The sera from all rabbits were studied each week for concentrations of circulating BSA and for capacity to bind 131I-labelled BSA or HSA (I*BSA or I*HSA). Some sera were also studied after fractionation on Sephadex G-200 columns to remove the BSA which had been present in vivo. Serum levels of BSA were determined and the binding studies performed using variations of the ammonium sulphate method to detect I* antigen—antibody complexes. Some sera were also studied by radioimmunoelectrophoresis.

The observed steady-state serum levels of circulating BSA during the daily infusions were substantially less than the theoretical concentrations. In addition, the measured BSA levels were particularly low throughout two periods of the experiment. The first occurred between days 14 and 35 when the rabbits had significant proteinuria and the second between days 45 and 66 when maximum antibody activity was observed. Following cessation of infusions, BSA disappeared from the circulation with a 5.5 day half-life.

Binding of I*BSA was not detected in whole serum but was measurable between days 14 and 165 after fractionation by gel filtration with Sephadex G-200 to remove the unlabelled BSA. In contrast, Sephadex filtration was not required to demonstrate I*HSA binding in whole serum between days 14 and 198, even in the presence of excess unlabelled BSA.

The immunological specificities of the antibodies present during `immunological paralysis' to BSA were characterized by comparing the effectiveness of graded amounts of unlabelled BSA or HSA to inhibit the I*BSA and I*HSA binding. The binding specificities of sera during `immunological paralysis' were found to be similar in certain respects but distinctly different in others from either normally produced anti-BSA or anti-HSA.

Rechallenge with 50 mg HSA on day 139 produced significant I*HSA binding but only slight I*BSA binding. Specificity studies on these antibodies revealed characteristics more typical of the normally produced anti-HSA than were observed during `immunological paralysis'. However, some characteristics of normally produced anti-BSA remained.

Rechallenge with BSA produced significant binding of either I*BSA or I*HSA, and in some cases both. Specificity studies of these antibodies revealed more of the characteristics of normally produced anti-BSA than were observed prior to rechallenge but some of the characteristics of normally produced anti-HSA remained.

These results indicate that rabbits receiving large daily injections of BSA are `immunologically suppressed' rather than `immunologically paralysed' to BSA. A hypothesis is presented to explain the coexistence of BSA and antibodies having the I* antigen binding characteristics observed in the serum of these `immunologically suppressed' rabbits.

Full text

PDF
571

Images in this article

578-1FIG. 5
on p.578-1

Selected References

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

  1. DIXON F. J., FELDMAN J. D., VAZQUEZ J. J. Experimental glomerulonephritis. The pathogenesis of a laboratory model resembling the spectrum of human glomerulonephritis. J Exp Med. 1961 May 1;113:899–920. doi: 10.1084/jem.113.5.899. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. DRESSER D. W. Specific inhibition of antibody production. II. Paralysis induced in adult mice by small quantities of protein antigen. Immunology. 1962 May;5:378–388. [PMC free article] [PubMed] [Google Scholar]
  3. FARR R. S. A quantitative immunochemical measure of the primary interaction between I BSA and antibody. J Infect Dis. 1958 Nov-Dec;103(3):239–262. doi: 10.1093/infdis/103.3.239. [DOI] [PubMed] [Google Scholar]
  4. FARR R. S., DIXON F. J., Jr The effect of antigen concentration on the initiation of detectable antibody synthesis in rabbits. J Immunol. 1960 Sep;85:250–257. [PubMed] [Google Scholar]
  5. HUMPHREY J. H. IMMUNOLOGICAL UNRESPONSIVENESS TO PROTEIN ANTIGENS IN RABBITS. I. THE DURATION OF UNRESPONSIVENESS FOLLOWING A SINGLE INJECTION AT BIRTH. Immunology. 1964 Jul;7:449–461. [PMC free article] [PubMed] [Google Scholar]
  6. LINSCOTT W. D. CONTAMINATION OF COMMERCIAL RABBIT ALBUMIN PREPARATIONS BY BOVINE ALBUMIN. Science. 1963 Nov 29;142(3596):1170–1172. doi: 10.1126/science.142.3596.1170. [DOI] [PubMed] [Google Scholar]
  7. MITCHISON N. A. INDUCTION OF IMMUNOLOGICAL PARALYSIS IN TWO ZONES OF DOSAGE. Proc R Soc Lond B Biol Sci. 1964 Dec 15;161:275–292. doi: 10.1098/rspb.1964.0093. [DOI] [PubMed] [Google Scholar]
  8. Rothberg R. M., Farr R. S. Antibodies in rabbits fed milk and their similarities to antibodies in some human sera. J Allergy. 1965 Sep-Oct;36(5):450–462. doi: 10.1016/0021-8707(65)90139-5. [DOI] [PubMed] [Google Scholar]
  9. SCHWARTZ R. S., DAMESHEK W. THE ROLE OF ANTIGEN DOSAGE IN DRUG-INDUCED IMMUNOLOGIC TOLERANCE. J Immunol. 1963 May;90:703–710. [PubMed] [Google Scholar]
  10. SMITH R. T., BRIDGES R. A. Immunological unresponsiveness in rabbits produced by neonatal injection of defined antigens. J Exp Med. 1958 Aug 1;108(2):227–250. doi: 10.1084/jem.108.2.227. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Sobey W. R., Magrath J. M. Acquired immunological unresponsiveness to bovine plasma albumin in mice. Aust J Biol Sci. 1965 Aug;18(4):947–951. doi: 10.1071/bi9650947. [DOI] [PubMed] [Google Scholar]
  12. WEIGLE W. O., DIXON F. J. Elimination of heterologous proteins from blood of normal, x-radiated and tolerant rabbits. Proc Soc Exp Biol Med. 1958 Jun;98(2):213–215. doi: 10.3181/00379727-98-23994. [DOI] [PubMed] [Google Scholar]
  13. WEIGLE W. O., DIXON F. J. The antibody response of lymph node cells transferred to tolerant recipients. J Immunol. 1959 Jun;82(6):516–519. [PubMed] [Google Scholar]
  14. WEIGLE W. O., McCONAHEY P. J. The serological cross-reaction between bovine serum albumin and anti-ovalbumin. J Immunol. 1962 Jan;88:121–127. [PubMed] [Google Scholar]
  15. WEIGLE W. O. STUDIES ON THE TERMINATION OF ACQUIRED TOLERANCE TO SERUM PROTEIN ANTIGENS FOLLOWING INJECTION OF SEROLOGICALLY RELATED ANTIGENS. Immunology. 1964 May;7:239–247. [PMC free article] [PubMed] [Google Scholar]
  16. WEIGLE W. O. THE IMMUNE RESPONSE OF BSA TOLERANT RABBITS TO INJECTIONS OF BSA FOLLOWING THE TERMINATION OF THE TOLERANT STATE. J Immunol. 1964 May;92:791–797. [PubMed] [Google Scholar]
  17. WEIGLE W. O. The immune response of rabbits tolerant to bovine serum albumin to the injection of other heterologous serum albumins. J Exp Med. 1961 Jul 1;114:111–125. doi: 10.1084/jem.114.1.111. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. WEIGLE W. O. The nature of antigen-antibody complexes formed in rabbits during an immune response to bovine serum albumin. J Exp Med. 1958 May 1;107(5):653–663. doi: 10.1084/jem.107.5.653. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. YAGI Y., MAIER P., PRESSMAN D., ARBESMAN C. E., REISMAN R. E. THE PRESENCE OF THE RAGWEED-BINDING ANTIBODIES IN THE BETA-2A, BETA-2M, AND GAMMA GLOBULINS OF THE SENSITIVE INDIVIDUALS. J Immunol. 1963 Jul;91:83–89. [PubMed] [Google Scholar]
  20. YALOW R. S., BERSON S. A. Immunologic aspects of insulin. Am J Med. 1961 Dec;31:882–891. doi: 10.1016/0002-9343(61)90030-4. [DOI] [PubMed] [Google Scholar]

Articles from Immunology are provided here courtesy of British Society for Immunology

RESOURCES