Skip to main content
NCBI home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1979 Jul 1;150(1):138–153. doi: 10.1084/jem.150.1.138

Production of auto-anti-idiotypic antibody during the normal immune response to TNP-ficoll. I. Occurrence in AKR/J and BALB/c mice of hapten-augmentable, anti-TNP plaque-forming cells and their accelerated appearance in recipients of immune spleen cells

AF Schrater, EA Goidl, GJ Thorbecke, GW Siskind
PMCID: PMC2185608  PMID: 312903

Abstract

Attempts were made to elucidate the cause of the downward regulation of the splenic plaque-forming cell (PFC) response in AKR/J and BALB/c mice between days 4 and 7 after a single intravenous injection of 2,4,6,trinitrophenyl- lys-Ficoll(TNP-F). AKR/J spleen cells, taken 7 d after injection of TNP-F, were transferred, together with TNP-F, into normal AKR/J mice. The day-3 or – 4 PFC response of the recipients was much lower than that of recipients of normal cells. However, the suppression was only apparent because the presence of 10(-8)-10(-7) M 2,4,6-trinitrophenyl-ε-amino-n-caproic acid (TNP- EACA) (or 10(-7)-10(-6) M 2,4,-dinitrophenyl-ε-amino-n-caproic acid) in the PFC assay caused a dramatic increase in observed PFC, averaging 298 percent on day 3 and 122 percent on day 4. Recipients of normal cells showed no such hapten-augmentable PFC. T-depleted immune spleen cells did not cause any apparent suppression of the response to TNP-F, but hapten-augmentable PFC in recipient spleens were again prevalent. Suppression of the PFC response, as well as hapten-augmentable PFC, were seen after transfer of immune serum. It was postulated that hapten augmentation of PFC was caused by displacement of auto-anti-idiotypic antibody from the surface of blocked antibody- synthesizing cells. Further studies showed that such hapten-augmentable PFC occurred in the spleens of a large percentage of both AKR/J and BALB/c mice examined after day 4 of the primary response to TNP-F. Thus, it was hypothesized that the downward regulation of the magnitude and, possibly, also of the heterogeneity of the splenic-PFC response was due to an auto-antibody response to one or more major idiotypes of the anti-TNP response.

Full Text

The Full Text of this article is available as a PDF (983.5 KB).

Selected References

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

  1. Andersson B. Studies on the regulation of avidity at the level of the single antibody-forming cell. The effect of antigen dose and time after immunization. J Exp Med. 1970 Jul 1;132(1):77–88. doi: 10.1084/jem.132.1.77. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bankert R. B., Pressman D. Receptor-blocking factor present in immune serum resembling auto-anti-idiotype antibody. J Immunol. 1976 Aug;117(2):457–462. [PubMed] [Google Scholar]
  3. Binz H., Wigzell H. Specific transplantation tolerance induced by autoimmunization against the individual's own, naturally occurring idiotypic, antigen-binding receptors. J Exp Med. 1976 Dec 1;144(6):1438–1457. doi: 10.1084/jem.144.6.1438. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cancro M. P., Sigal N. H., Klinman N. R. Differential expression of an equivalent clonotype among BALB/c and C57BL/6 mice. J Exp Med. 1978 Jan 1;147(1):1–12. doi: 10.1084/jem.147.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cosenza H. Detection of anti-idiotype reactive cells in the response to phosphorylcholine. Eur J Immunol. 1976 Feb;6(2):114–116. doi: 10.1002/eji.1830060208. [DOI] [PubMed] [Google Scholar]
  6. Cosenza H., Köhler H. Specific inhibition of plaque formation to phosphorylcholine by antibody against antibody. Science. 1972 Jun 2;176(4038):1027–1029. doi: 10.1126/science.176.4038.1027. [DOI] [PubMed] [Google Scholar]
  7. DeLisi C., Goldstein B. On the mechanism of hemolytic plaque inhibition. Immunochemistry. 1974 Oct;11(10):661–665. doi: 10.1016/0019-2791(74)90223-7. [DOI] [PubMed] [Google Scholar]
  8. Doria G., Mancini C., DeLisi C. Secretion rate independent evaluation of IgM antibody avidity at the level of single immunocytes. J Immunol. 1978 Nov;121(5):2030–2034. [PubMed] [Google Scholar]
  9. Doria G., Schiaffini G., Garavini M., Mancini C. The rise and fall of antibody avidity at the level of single immunocytes. J Immunol. 1972 Dec;109(6):1245–1253. [PubMed] [Google Scholar]
  10. Dresser D. W., Wortis D. H. Use of an antiglobulin serum to detect cells producing antibody with low haemolytic efficiency. Nature. 1965 Nov 27;208(5013):859–861. doi: 10.1038/208859a0. [DOI] [PubMed] [Google Scholar]
  11. Eichmann K. Idiotypic identity of antibodies to streptococcal carbohydrate in inbred mice. Eur J Immunol. 1972 Aug;2(4):301–307. doi: 10.1002/eji.1830020402. [DOI] [PubMed] [Google Scholar]
  12. Gearhart P. J., Cebra J. J. Idiotype sharing by murine strains differing in immunoglobulin allotype. Nature. 1978 Mar 16;272(5650):264–265. doi: 10.1038/272264a0. [DOI] [PubMed] [Google Scholar]
  13. Gershwin M. E., Merchant B., Steinberg A. D. The effects of synthetic polymeric agents on immune responses of nude mice. Immunology. 1977 Mar;32(3):327–336. [PMC free article] [PubMed] [Google Scholar]
  14. Goidl E. A., Birnbaum G., Siskind G. W. Determination of antibody avidity at the cellular level by the plaque inhibition technique: effect of valence of the inhibitor. J Immunol Methods. 1975;8(1-2):47–45. doi: 10.1016/0022-1759(75)90080-0. [DOI] [PubMed] [Google Scholar]
  15. Goidl E. A., Schrater A. F., Siskind G. W., Thorbecke G. J. Production of auto-anti-idiotypic antibody during the normal immune response to TNP-Ficoll. II. Hapten-reversible inhibition of anti-TNP plaque-forming cells by immune serum as an assay for auto-anti-idiotypic antibody. J Exp Med. 1979 Jul 1;150(1):154–165. doi: 10.1084/jem.150.1.154. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Goidl E. A., Siskind G. W. Ontogeny of B-lymphocyte function. I. Restricted heterogeneity of the antibody response of B lymphocytes from neonatal and fetal mice. J Exp Med. 1974 Nov 1;140(5):1285–1302. doi: 10.1084/jem.140.5.1285. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Golub E. S. Brain-associated theta antigen: reactivity of rabbit anti-mouse brain with mouse lymphoid cells. Cell Immunol. 1971 Aug;2(4):353–361. doi: 10.1016/0008-8749(71)90070-0. [DOI] [PubMed] [Google Scholar]
  18. Hart D. A., Wang A. L., Pawlak L. L., Nisonoff A. Suppression of idiotypic specificities in adult mice by administration of antiidiotypic antibody. J Exp Med. 1972 Jun 1;135(6):1293–1300. doi: 10.1084/jem.135.6.1293. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Janeway C. A., Jr, Paul W. E. Hapten-specific augmentation of the anti-idiotype antibody response to hapten-myeloma protein conjugates in mice. Eur J Immunol. 1973 Jun;3(6):340–347. doi: 10.1002/eji.1830030605. [DOI] [PubMed] [Google Scholar]
  20. Jerne N. K. Towards a network theory of the immune system. Ann Immunol (Paris) 1974 Jan;125C(1-2):373–389. [PubMed] [Google Scholar]
  21. Kipps T. J., Benacerraf B., Dorf M. E. Presence of common idiotypes on antibodies induced by glutamic acid-lysine-containing terpolymers in responder and nonresponder mice with the Ig-1b heavy chain allotype. Eur J Immunol. 1977 Dec;7(12):865–871. doi: 10.1002/eji.1830071209. [DOI] [PubMed] [Google Scholar]
  22. Klaus G. G. Antigen-antibody complexes elicit anti-idiotypic antibodies to self-idiotopes. Nature. 1978 Mar 16;272(5650):265–266. doi: 10.1038/272265a0. [DOI] [PubMed] [Google Scholar]
  23. Klinman N. R., Press J. L., Segal G. P. Overlap stimulation of primary and secondary B cells by cross-reacting determinants. J Exp Med. 1973 Nov 1;138(5):1276–1281. doi: 10.1084/jem.138.5.1276. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Kluskens L., Köhler H. Regulation of immune response by autogenous antibody against receptor. Proc Natl Acad Sci U S A. 1974 Dec;71(12):5083–5087. doi: 10.1073/pnas.71.12.5083. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. 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]
  26. Lerman S. P., Romano T. J., Mond J. J., Heidelberger M., Thorbecke G. J. Induction of primary and inhibition of secondary antibody response to hapten by hapten conjugates of type III pneumococcal polysaccharide. Cell Immunol. 1975 Feb;15(2):321–335. doi: 10.1016/0008-8749(75)90011-8. [DOI] [PubMed] [Google Scholar]
  27. Little J. R., Eisen H. N. Preparation and characterization of antibodies specific for the 2,4,6-trinitrophenyl group. Biochemistry. 1966 Nov;5(11):3385–3395. doi: 10.1021/bi00875a001. [DOI] [PubMed] [Google Scholar]
  28. 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]
  29. McKearn T. J., Stuart F. P., Fitch F. W. Anti-idiotypic antibody in rat transplantation immunity. I. Production of anti-idiotypic antibody in animals repeatedly immunized with alloantigens. J Immunol. 1974 Dec;113(6):1876–1882. [PubMed] [Google Scholar]
  30. Mitchell G. F., Humphrey J. H., Wiliamson A. R. Inhibition of secondary anti-hapten responses with the hapten conjugated to type 3 pneumococcal polysaccharide. Eur J Immunol. 1972 Oct;2(5):460–467. doi: 10.1002/eji.1830020516. [DOI] [PubMed] [Google Scholar]
  31. NAJJAR V. A. Some aspects of antibody-antigen reactions and theoretical considerations of the immunologic response. Physiol Rev. 1963 Apr;43:243–262. doi: 10.1152/physrev.1963.43.2.243. [DOI] [PubMed] [Google Scholar]
  32. Neri R., Pini C., Vicari G., Doria G. Time and antigen dose-dependent variations of IgM antibody affinity. Eur J Immunol. 1978 Nov;8(11):823–825. doi: 10.1002/eji.1830081114. [DOI] [PubMed] [Google Scholar]
  33. Nisonoff A., Ju S. T., Owen F. L. Studies of structure and immunosuppression of cross-reactive idiotype in strain A mice. Immunol Rev. 1977;34:89–118. doi: 10.1111/j.1600-065x.1977.tb00369.x. [DOI] [PubMed] [Google Scholar]
  34. Näkelä O., Kaartinen M., Pelkonen J. L., Karjalainen K. Inheritance of antibody specificity V. Anti-2-phenyloxazolone in the mouse. J Exp Med. 1978 Dec 1;148(6):1644–1660. doi: 10.1084/jem.148.6.1644. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. OUDIN J., MICHEL M. [A new allotype form of rabbit serum gamma-globulins, apparently associated with antibody function and specificity]. C R Hebd Seances Acad Sci. 1963 Jul 17;257:805–808. [PubMed] [Google Scholar]
  36. Pierce S. K., Klinman N. R. Antibody-specific immunoregulation. J Exp Med. 1977 Aug 1;146(2):509–519. doi: 10.1084/jem.146.2.509. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. REIF A. E., ALLEN J. M. THE AKR THYMIC ANTIGEN AND ITS DISTRIBUTION IN LEUKEMIAS AND NERVOUS TISSUES. J Exp Med. 1964 Sep 1;120:413–433. doi: 10.1084/jem.120.3.413. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Rittenberg M. B., Pratt K. L. Antitrinitrophenyl (TNP) plaque assay. Primary response of Balb/c mice to soluble and particulate immunogen. Proc Soc Exp Biol Med. 1969 Nov;132(2):575–581. doi: 10.3181/00379727-132-34264. [DOI] [PubMed] [Google Scholar]
  39. Rodkey L. S. Studies of idiotypic antibodies. Production and characterization of autoantiidiotypic antisera. J Exp Med. 1974 Mar 1;139(3):712–720. doi: 10.1084/jem.139.3.712. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Rodkey L. S. Studies of idiotypic antibodies: reactions of isologous and autologous anti-idiotypic antibodies with the same antibody preparations. J Immunol. 1976 Sep;117(3):986–989. [PubMed] [Google Scholar]
  41. Rowley D. A., Fitch F. W., Stuart F. P., Köhler H., Cosenza H. Specific suppression of immune responses. Science. 1973 Sep 21;181(4105):1133–1141. doi: 10.1126/science.181.4105.1133. [DOI] [PubMed] [Google Scholar]
  42. Rowley D. A., Köhler H., Schreiber H., Kaye S. T., Lorbach I. Suppression by autogenous complementary idiotypes: the priority of the first response. J Exp Med. 1976 Oct 1;144(4):946–959. doi: 10.1084/jem.144.4.946. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Sakato N., Eisen H. N. Antibodies to idiotypes of isologous immunoglobulins. J Exp Med. 1975 Jun 1;141(6):1411–1426. doi: 10.1084/jem.141.6.1411. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Sharon R., McMaster P. R., Kask A. M., Owens J. D., Paul W. E. DNP-Lys-ficoll: a T-independent antigen which elicits both IgM and IgG anti-DNP antibody-secreting cells. J Immunol. 1975 May;114(5):1585–1589. [PubMed] [Google Scholar]
  45. Sirisinha S., Eisen H. N. Autoimmune-like antibodies to the ligand-binding sites of myeloma proteins. Proc Natl Acad Sci U S A. 1971 Dec;68(12):3130–3135. doi: 10.1073/pnas.68.12.3130. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Stevens R. W., Ziegler F. D., Kelly J. H. Detection of serum-hepatitis antigen by charcoal particle agglutination-inhibition. J Immunol. 1972 Apr;108(4):1119–1122. [PubMed] [Google Scholar]
  47. Tasiaux N., Leuwenkroon R., Bruyns C., Urbain J. Possible occurrence and meaning of lymphocytes bearing autoanti-idiotypic receptors during the immune response. Eur J Immunol. 1978 Jul;8(7):464–468. doi: 10.1002/eji.1830080704. [DOI] [PubMed] [Google Scholar]
  48. Urbain J. Idiotypes, expression of antibody diversity and network concepts. Ann Immunol (Paris) 1976 Jun-Jul;127(3-4):357–374. [PubMed] [Google Scholar]
  49. Weigle W. O. Cyclical production of antibody as a regulatory mechanism in the immune response. Adv Immunol. 1975;21:87–111. doi: 10.1016/s0065-2776(08)60219-9. [DOI] [PubMed] [Google Scholar]
  50. Werblin T. P., Kim Y. T., Quagliata F., Siskind G. W. Studies on the control of antibody synthesis. 3. Changes in heterogeneity of antibody affinity during the course of the immune response. Immunology. 1973 Mar;24(3):477–492. [PMC free article] [PubMed] [Google Scholar]
  51. Wigzell H. Antibody synthesis at the cellular level. Antibody-induced suppression of 7S antibody synthesis. J Exp Med. 1966 Nov 1;124(5):953–969. doi: 10.1084/jem.124.5.953. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Woodland R., Cantor H. Idiotype-specific T helper cells are required to induce idiotype-positive B memory cells to secrete antibody. Eur J Immunol. 1978 Aug;8(8):600–606. doi: 10.1002/eji.1830080812. [DOI] [PubMed] [Google Scholar]

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

RESOURCES