Skip to main content
NCBI home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1980 May;65(5):1202–1209. doi: 10.1172/JCI109775

Regulation of monoclonal immunoglobulin G synthesis by antiidiotypic antibody in a patient with hypogammaglobulinemia.

F Mudawwar, Z Awdeh, K Ault, R S Geha
PMCID: PMC371454  PMID: 6767740

Abstract

The regulation of in vitro antibody synthesis by antiidiotypic antibodies was studied in a child with hypogammaglobulinemia and a serum immunoglobulin (Ig)G1 kappa M component. A rabbit antiserum was raised against the purified M component and was rendered idiotype specific by extensive absorption with Cohn fraction II and with IgG derived from the patient's parents. Hemagglutination-inhibition studies demonstrated that less than 1 in 300,000 molecules of pooled human IgG carried M component-related idiotypic determinants. 12% of the patient's B cells, but none of her T cells, expressed idiotypic determinants on their surface. Spontaneous de novo synthesis of the M component by the patient's peripheral blood lymphocytes was demonstrated in vitro and was shown to proceed independently of the polyclonal activator pokeweed mitogen. Antiidiotypic rabbit IgG, but not its F(ab')2, fragments, profoundly inhibited the synthesis of M component by the patient's peripheral blood lymphocytes. We concluded that antiidiotypic antibodies may play a role in the regulation of antibody synthesis in man.

Full text

PDF
1202

Selected References

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

  1. Abbas A. K. Inhibition of antibody production in plasmacytoma cells. III. Interactions of suppressive and nonsuppressive DNP conjugates with MOPC 315 cells. J Immunol. 1979 May;122(5):1791–1797. [PubMed] [Google Scholar]
  2. Ault K. A. Detection of small numbers of monoclonal B lymphocytes in the blood of patients with lymphoma. N Engl J Med. 1979 Jun 21;300(25):1401–1405. doi: 10.1056/NEJM197906213002501. [DOI] [PubMed] [Google Scholar]
  3. Awdeh Z. L., Williamson A. R., Askonas B. A. Isoelectric focusing in polyacrylamide gel and its application to immunoglobulins. Nature. 1968 Jul 6;219(5149):66–67. doi: 10.1038/219066a0. [DOI] [PubMed] [Google Scholar]
  4. Bona C., Lieberman R., House S., Green I., Paul W. E. Immune response to levan. II. T independence of suppression of cross-reactive idiotypes by anti-idiotype antibodies. J Immunol. 1979 Apr;122(4):1614–1619. [PubMed] [Google Scholar]
  5. Brown J. C., Rodkey L. S. Autoregulation of an antibody response via network-induced auto-anti-idiotype. J Exp Med. 1979 Jul 1;150(1):67–85. doi: 10.1084/jem.150.1.67. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. 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]
  7. Cosenza H., Julius M. H., Augustin A. A. Idiotypes as variable region markers: analogies between receptors on phosphorylcholine-specific T and B lymphocytes. Immunol Rev. 1977;34:3–33. doi: 10.1111/j.1600-065x.1977.tb00366.x. [DOI] [PubMed] [Google Scholar]
  8. 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]
  9. Eichmann K., Rajewsky K. Induction of T and B cell immunity by anti-idiotypic antibody. Eur J Immunol. 1975 Oct;5(10):661–666. doi: 10.1002/eji.1830051002. [DOI] [PubMed] [Google Scholar]
  10. Geha R. S., Hyslop N., Alami S., Farah F., Schneeberger E. E., Rosen F. S. Hyper immunoglobulin M immunodeficiency. (Dysgammaglobulinemia). Presence of immunoglobulin M-secreting plasmacytoid cells in peripheral blood and failure of immunoglobulin M-immunoglobulin G switch in B-cell differentiation. J Clin Invest. 1979 Aug;64(2):385–391. doi: 10.1172/JCI109473. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Geha R. S., Schneeberger E., Gatien J., Rosen F. S., Merler E. Synthesis of an M component by circulating B lymphocytes in severe combined immunodeficiency. N Engl J Med. 1974 Mar 28;290(13):726–728. doi: 10.1056/NEJM197403282901308. [DOI] [PubMed] [Google Scholar]
  12. Geha R. S., Weinberg R. P. Anti-idiotypic antisera in man. I. Production and immunochemical characterization of anti-idiotypic antisera to human antitetanus antibodies. J Immunol. 1978 Oct;121(4):1518–1523. [PubMed] [Google Scholar]
  13. Goding J. W. The chromic chloride method of coupling antigens to erythrocytes: definition of some important parameters. J Immunol Methods. 1976;10(1):61–66. doi: 10.1016/0022-1759(76)90007-7. [DOI] [PubMed] [Google Scholar]
  14. Griscelli C., Desmonts G., Gny B., Frommel D. Congenital toxoplasmosis. Fetal synthesis of oligoclonal immunoglobulin G in intrauterine infection. J Pediatr. 1973 Jul;83(1):20–26. doi: 10.1016/s0022-3476(73)80306-3. [DOI] [PubMed] [Google Scholar]
  15. Holm G., Mellstedt H., Pettersson D., Biberfeld R. Idiotypic immunoglobulin structures on blood lymphocytes in human plasma cell myeloma. Immunol Rev. 1977;34:139–164. doi: 10.1111/j.1600-065x.1977.tb00371.x. [DOI] [PubMed] [Google Scholar]
  16. Hunter R. Standardization of the chloramine-T method of protein iodination. Proc Soc Exp Biol Med. 1970 Mar;133(3):989–992. doi: 10.3181/00379727-133-34611. [DOI] [PubMed] [Google Scholar]
  17. 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]
  18. Köhler H., Richardson B. C., Rowley D. A., Smyk S. Immune response to phosphorylcholine. III. Requirement of the Fc portion and equal effectiveness of IgG subclasses in anti-receptor antibody-induced suppression. J Immunol. 1977 Dec;119(6):1979–1986. [PubMed] [Google Scholar]
  19. Lea T., Førre O. T., Michaelsen T. E., Natvig J. B. Shared idiotypes of human peripheral blood B and T lymphocytes. J Immunol. 1979 Jun;122(6):2413–2417. [PubMed] [Google Scholar]
  20. Mellstedt H., Pettersson D., Holm G. Monoclonal B-lymphocytes in peripheral blood of patients with plasma cell myeloma. Relation to activity of the disease. Scand J Haematol. 1976 Feb;16(2):112–120. doi: 10.1111/j.1600-0609.1976.tb01125.x. [DOI] [PubMed] [Google Scholar]
  21. Owen F. L., Ju S. T., Nisonoff A. Presence on idiotype-specific suppressor T cells of receptors that interact with molecules bearing the idiotype. J Exp Med. 1977 Jun 1;145(6):1559–1566. doi: 10.1084/jem.145.6.1559. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Preud'homme J. L., Klein M., Labaume S., Seligmann M. Idiotype-bearing and antigen-binding receptors produced by blood T lymphocytes in a case of human myeloma. Eur J Immunol. 1977 Dec;7(12):840–846. doi: 10.1002/eji.1830071204. [DOI] [PubMed] [Google Scholar]
  23. Rohrer J. W., Odermatt B., Lynch R. G. Immunoregulation of murine myeloma: isologous immunization with M315 induces idiotype-specific T cells that suppress IgA secretion by MOPC-315 cells in vivo. J Immunol. 1979 May;122(5):2011–2019. [PubMed] [Google Scholar]
  24. Schrater A. F., Goidl E. A., Thorbecke G. J., Siskind G. W. 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. J Exp Med. 1979 Jul 1;150(1):138–153. doi: 10.1084/jem.150.1.138. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Winkler M., Franssen J. D., Collignon C., Leo O., Mariamé B., van de Walle P., de Groote D., Urbain J. Idiotypic regulation of the immune system. Common idiotypic specificities between idiotypes and antibodies raised against anti-idiotypic antibodies in rabbits. J Exp Med. 1979 Jul 1;150(1):184–195. doi: 10.1084/jem.150.1.184. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES