Skip to main content
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1971 May 1;133(5):987–1003. doi: 10.1084/jem.133.5.987

REGULATION OF THE IMMUNE RESPONSE: SUPPRESSIVE AND ENHANCING EFFECTS OF PASSIVELY ADMINISTERED ANTIBODY

Carolyn S Pincus 1, Michael E Lamm 1, Victor Nussenzweig 1
PMCID: PMC2138911  PMID: 4101806

Abstract

The ability of passively administered antibody to suppress the immune response against homologous antigenic determinants while concomitantly enhancing the response against other unrelated determinants of the same antigen molecule has been established in two distinct antigen-antibody systems: (a) guinea pig γ2-immunoglobulin + passive anti-F(ab')2 antibody, where suppression of anti-F(ab')2 antibody synthesis is accompanied by enhancement of the anti-Fc response; and (b) human secretory IgA + passive anti-serum IgA antibody, where suppression of antibody production against the α and L chains accompanies augmentation of the response to the secretory component. The mechanisms of the suppressive and enhancing effects are probably unrelated for the following reasons: (a) Enhancement of the response to certain determinants may be obtained without discernible suppression of the response to the homologous determinants; and (b) the F(ab')2 fragments of passive antibody can mediate immune suppression but were not observed to enhance the response against the unrelated determinants of the same antigen molecule. Also, the timing for achieving maximum suppression or enhancement of antibody formation is not the same; enhancement was obtained only at a later time. Both the enhancement and suppressive effects were obtained with the purified γG fraction of antisera. This finding rules out an exclusive role of γM antibody in the enhancement phenomenon.

Full Text

The Full Text of this article is available as a PDF (953.6 KB).

Selected References

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

  1. Bistany T. S., Tomasi T. B., Jr Serum and secretory immunoglobulins of the rat. Immunochemistry. 1970 May;7(5):453–460. doi: 10.1016/0019-2791(70)90227-2. [DOI] [PubMed] [Google Scholar]
  2. Brody N. I., Walker J. G., Siskind G. W. Studies on the control of antibody synthesis. Interaction of antigenic competition and suppression of antibody formation by passive antibody on the immune response. J Exp Med. 1967 Jul 1;126(1):81–91. doi: 10.1084/jem.126.1.81. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Cebra J. J., Robbins J. B. Gamma-A-immunoglobulin from rabbit colostrum. J Immunol. 1966 Jul;97(1):12–24. [PubMed] [Google Scholar]
  4. Cerottini J. C., McConahey P. J., Dixon F. J. Specificity of the immunosuppression caused by passive administration of antibody. J Immunol. 1969 Aug;103(2):268–275. [PubMed] [Google Scholar]
  5. Cerottini J. C., McConahey P. J., Dixon F. J. The immunosuppressive effect of passively administered antibody IgG fragments. J Immunol. 1969 Apr;102(4):1008–1015. [PubMed] [Google Scholar]
  6. Chang H., Schneck S., Brody N. I., Deutsch A., Siskind G. W. Studies on the mechanism of the suppression of active antibody synthesis by passively administered antibody. J Immunol. 1969 Jan;102(1):37–41. [PubMed] [Google Scholar]
  7. Cohn M., Notani G., Rice S. A. Characterization of the antibody to the C-carbohydrate produced by a transplantable mouse plasmacytoma. Immunochemistry. 1969 Jan;6(1):111–123. doi: 10.1016/0019-2791(69)90183-9. [DOI] [PubMed] [Google Scholar]
  8. Czajkowski N. P., Rosenblatt M., Cushing F. R., Vazquez J., Wolf P. L. Production of active immunity to malignant neoplastic tissue. Chemical coupling to an antigenic protein carrier. Cancer. 1966 Jun;19(6):739–749. doi: 10.1002/1097-0142(196606)19:6<739::aid-cncr2820190602>3.0.co;2-q. [DOI] [PubMed] [Google Scholar]
  9. Dixon F. J., Jacot-Guillarmod H., McConahey P. J. The effect of passively administered antibody on antibody synthesis. J Exp Med. 1967 Jun 1;125(6):1119–1135. doi: 10.1084/jem.125.6.1119. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Dukor P., Bianco C., Nussenzweig V. Tissue localization of lymphocytes bearing a membrane receptor for antigen-antibody-complement complexes. Proc Natl Acad Sci U S A. 1970 Oct;67(2):991–997. doi: 10.1073/pnas.67.2.991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. EISEN H. N., CARSTEN M. E., BELMAN S. Studies of hypersensitivity to low molecular weight substances. III. The 2,4-dinitrophenyl group as a determinant in the preciptin reaction. J Immunol. 1954 Nov;73(5):296–308. [PubMed] [Google Scholar]
  12. Fink C. W., LoSpalluto J. J. The effect of 7S and 19S antibodies on the primary response to Salmonella typhi antigens. Immunology. 1967 Mar;12(3):259–266. [PMC free article] [PubMed] [Google Scholar]
  13. Henney C. S., Ishizaka K. Studies on the immunogenicity of antigen-antibody precipitates. 1. The suppressive effect of anti-L and anti-H chain antibodies on the immunogenicity of human gammaG globulin. J Immunol. 1968 Nov;101(5):896–904. [PubMed] [Google Scholar]
  14. Henry C., Jerne N. K. Competition of 19S and 7S antigen receptors in the regulation of the primary immune response. J Exp Med. 1968 Jul 1;128(1):133–152. doi: 10.1084/jem.128.1.133. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. ISSITT P. D. ON THE INCIDENCE OF SECOND ANTIBODY POPULATIONS IN THE SERA OF WOMEN WHO HAVE DEVELOPED ANTI-RH ANTIBODIES. Transfusion. 1965 Jul-Aug;5:355–358. doi: 10.1111/j.1537-2995.1965.tb01185.x. [DOI] [PubMed] [Google Scholar]
  16. Katz D. H., Paul W. E., Goidl E. A., Benacerraf B. Carrier function in anti-hapten immune responses. I. Enhancement of primary and secondary anti-hapten antibody responses by carrier preimmunization. J Exp Med. 1970 Aug 1;132(2):261–282. doi: 10.1084/jem.132.2.261. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. MOLLER G., WIGZELL H. ANTIBODY SYNTHESIS AT THE CELLULAR LEVEL. ANTIBODY-INDUCED SUPPRESSION OF 19S AND 7S ANTIBODY RESPONSE. J Exp Med. 1965 Jun 1;121:969–989. doi: 10.1084/jem.121.6.969. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. MULLER-EBERHARD H. J., KUNKEL H. G. The carbohydrate of gamma-globulin and myeloma proteins. J Exp Med. 1956 Aug 1;104(2):253–269. doi: 10.1084/jem.104.2.253. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. MacDonald A. B., Nisonoff A. Quantitative investigations of idiotypic antibodies. 3. Persistence and variations of idiotypic specificities during the course of immunization. J Exp Med. 1970 Mar 1;131(3):583–601. doi: 10.1084/jem.131.3.583. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. McBride R. A., Schierman L. W. Hapten-carrier relationships of isoantigens. A model for immunological maturation based on the conversion of haptens of carriers by antibody. J Exp Med. 1970 Feb;131(2):377–390. doi: 10.1084/jem.131.2.377. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Mitchell J., Abbot A. Ultrastructure of the antigen-retaining reticulum of lymph node follicles as shown by high-resolution autoradiography. Nature. 1965 Oct 30;208(5009):500–502. doi: 10.1038/208500b0. [DOI] [PubMed] [Google Scholar]
  22. OETTGEN H. F., BINAGHI R. A., BENACERRAF B. HEXOSE CONTENT OF GUINEA PIG GAMMA-1 AND GAMMA-2 IMMUNOGLOBULINS. Proc Soc Exp Biol Med. 1965 Feb;118:336–342. [PubMed] [Google Scholar]
  23. Pearlman D. S. The influence of antibodies on immunologic responses. I. The effect on the response to particulate antigen in the rabbit. J Exp Med. 1967 Jul 1;126(1):127–148. doi: 10.1084/jem.126.1.127. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Pincus C. S., Nussenzweig V. Passive antibody may simultaneously suppress and stimulate antibody formation against different portions of a protein molecule. Nature. 1969 May 10;222(5193):594–596. doi: 10.1038/222594a0. [DOI] [PubMed] [Google Scholar]
  25. Pollack W., Gorman J. G., Hager H. J., Freda V. J., Tripodi D. Antibody-mediated immune suppression to the Rh factor: animal models suggesting mechanism of action. Transfusion. 1968 May-Jun;8(3):134–145. doi: 10.1111/j.1537-2995.1968.tb04891.x. [DOI] [PubMed] [Google Scholar]
  26. ROWLEY D. A., FITCH F. W. HOMEOSTASIS OF ANTIBODY FORMATION IN THE ADULT RAT. J Exp Med. 1964 Dec 1;120:987–1005. doi: 10.1084/jem.120.6.987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Rajewsky K., Rottländer E., Peltre G., Müller B. The immune response to a hybrid protein molecule; specificity of secondary stimulation and of tolerance induction. J Exp Med. 1967 Oct 1;126(4):581–606. doi: 10.1084/jem.126.4.581. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Rajewsky K., Schirrmacher V., Nase S., Jerne N. K. The requirement of more than one antigenic determinant for immunogenicity. J Exp Med. 1969 Jun 1;129(6):1131–1143. doi: 10.1084/jem.129.6.1131. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. SALVIN S. B., SMITH R. F. Specificity of allergic reactions. II. Azoproteins in the anamnestic response. Proc Soc Exp Biol Med. 1960 Aug-Sep;104:584–590. doi: 10.3181/00379727-104-25916. [DOI] [PubMed] [Google Scholar]
  30. SALVIN S. B., SMITH R. F. The specificity of allergic reactions. I. Delayed versus Arthus hypersensitivity. J Exp Med. 1960 Apr 1;111:465–483. doi: 10.1084/jem.111.4.465. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. SPIEGELBERG H. L., WEIGLE W. O. THE CATABOLISM OF HOMOLOGOUS AND HETEROLOGOUS 7S GAMMA GLOBULIN FRAGMENTS. J Exp Med. 1965 Mar 1;121:323–338. doi: 10.1084/jem.121.3.323. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Schierman L. W., Leckband E., McBride R. A. Immunological interaction of erythrocyte isoantigens: effects of passive antibody. Proc Soc Exp Biol Med. 1969 Mar;130(3):744–747. doi: 10.3181/00379727-130-33646. [DOI] [PubMed] [Google Scholar]
  33. Schierman L. W., McBride R. A. Adjuvant activity of erythrocyte isoantigens. Science. 1967 May 5;156(3775):658–659. doi: 10.1126/science.156.3775.658. [DOI] [PubMed] [Google Scholar]
  34. Tao T. W., Uhr J. W. Capacity of pepsin-digested antibody to inhibit antibody formation. Nature. 1966 Oct 8;212(5058):208–209. doi: 10.1038/212208a0. [DOI] [PubMed] [Google Scholar]
  35. Tomasi T. B., Jr, Bienenstock J. Secretory immunoglobulins. Adv Immunol. 1968;9:1–96. doi: 10.1016/s0065-2776(08)60441-1. [DOI] [PubMed] [Google Scholar]
  36. Waldman R. H., Mach J. P., Stella M. M., Rowe D. S. Secretory IgA in human serum. J Immunol. 1970 Jul;105(1):43–47. [PubMed] [Google Scholar]
  37. Watkins J. F., Chen L. Immunization of mice against Ehrlich ascites tumour using a hamster-Ehrlich ascites tumour hybrid cell line. Nature. 1969 Sep 6;223(5210):1018–1022. doi: 10.1038/2231018a0. [DOI] [PubMed] [Google Scholar]
  38. Wolf P. L., Vazquez J., Czajkowski N. P., Rosenblatt M. A new method of active immunisation to autologous human tumour tissue. Lancet. 1967 Oct 28;2(7522):905–909. doi: 10.1016/s0140-6736(67)90229-2. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES