Skip to main content
NCBI home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1981 May 1;153(5):1173–1186. doi: 10.1084/jem.153.5.1173

Idiotype profile of an immune response. I. Contrasts in idiotypic dominance between primary and secondary responses and between IgM and IgG plaque- forming cells

JD Conger, GK Lewis, JW Goodman
PMCID: PMC2186146  PMID: 7019378

Abstract

The primary response of A/J mice to p-azobenzenearsonate-keyhole limpet hemocyanin (ABA-KLH) was investigated. A day-by-day analysis at the plaque- forming cell (PFC) level was performed, with inhibition by anti-cross- reactive idiotype (CRI) serum to determine percentage of CRI(+) PFC. A regular pattern in the dynamics of Id (idiotype) dominance was observed. Just as in the NP-b and NP-a systems (9, 12), the major Id (CRI) is more dominant in primary than in secondary or hyperimmune responses. This trend is more apparent in IgG PFC which are generally 80-95 percent CRI(+) at day 10 in the primary response but only 30-40 percent CRI(+) at day 10 in secondary or hyperimmune responses. A somewhat different pattern is seen with IgM PFC. These may reach a peak of 85 percent CRI(+) in the primary response, but secondary or hyperimmune IgM PFC, which are lower in numbers than IgG PFC, remain high in CRI content at approximately 70 percent. The PFC data on extent of id dominance in secondary or hyperimmune responses is fully compatible with previously reported serological data by others. Analysis of IgG PFC by hapten inhibition indicated that heterogeneity was in the order secondary PFC {greater than} primary PFC {greater than} hybridoma AK-2.2 PFC with H(75)/H(25) values of 22.9, 6.2, and 2.7, respectively; where H(75) and H(25) are the hapten concentrations required to give 75 percent and 25 percent of inhibition of PFC, respectively. Hapten inhibition data also suggested that secondary IgG PFC were 10 times higher in median binding avidity for ABA-L-tyrosine than primary IgG PFC. The kinetic analysis strongly indicated that CRI(+) IgM PFC were preferentially switched to IgG PFC in the primary response. In both studies, the CRI content of the earliest-appearing IgG PFC was significantly higher than that of IgM PFC on that day. For example, in one case IgM PFC were 60 percent CRI + on day 6 whereas IgG PFC were 100 percent CRI(+). The high Id dominance and selective isotype switching may have either a B or a T cell basis.

Full Text

The Full Text of this article is available as a PDF (925.9 KB).

Selected References

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

  1. Alkan S. S., Williams E. B., Nitecki D. E., Goodman J. W. Antigen recognition and the immune response. Humoral and cellular immune responses to small mono- and bifunctional antigen molecules. J Exp Med. 1972 Jun 1;135(6):1228–1246. doi: 10.1084/jem.135.6.1228. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Andersson J., Coutinho A., Melchers F. The switch from IgM to IgG secretion in single mitogen-stimulated B-cell clones. J Exp Med. 1978 Jun 1;147(6):1744–1754. doi: 10.1084/jem.147.6.1744. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bottomly K., Mathieson B. J., Mosier D. E. Anti-idiotype induced regulation of helper cell function for the response to phosphorylcholine in adult BALB/c mice. J Exp Med. 1978 Nov 1;148(5):1216–1227. doi: 10.1084/jem.148.5.1216. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Capra J. D., Nisonoff A. Structural studies on induced antibodies with defined idiotypic specificities. VII. The complete amino acid sequence of the heavy chain variable region of anti-p-azophenylarsenate antibodies from A/J mice bearing a cross-reactive idiotype. J Immunol. 1979 Jul;123(1):279–284. [PubMed] [Google Scholar]
  5. Claflin J. L., Lieberman R., Davie J. M. Clonal nature of the immune response to phosphorylcholine. II. Idiotypic specificity and binding characteristics of anti-phosphorylcholine antibodies. J Immunol. 1974 May;112(5):1747–1756. [PubMed] [Google Scholar]
  6. Claflin J. L. Uniformity in the clonal repertoire for the immune response to phosphorylcholine in mice. Eur J Immunol. 1976 Oct;6(10):669–674. doi: 10.1002/eji.1830061002. [DOI] [PubMed] [Google Scholar]
  7. Davie J. M., Paul W. E. Receptors on immunocompetent cells. V. Cellular correlates of the "maturation" of the immune response. J Exp Med. 1972 Mar 1;135(3):660–674. doi: 10.1084/jem.135.3.660. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. DeLisi C. Hemolytic plaque inhibition: the physical chemical limits on its use as an affinity assay. J Immunol. 1976 Dec;117(6):2249–2257. [PubMed] [Google Scholar]
  9. Eichmann K. Idiotype suppression. I. Influence of the dose and of the effector functions of anti-idiotypic antibody on the production of an idiotype. Eur J Immunol. 1974 Apr;4(4):296–302. doi: 10.1002/eji.1830040413. [DOI] [PubMed] [Google Scholar]
  10. Engvall E., Perlmann P. Enzyme-linked immunosorbent assay, Elisa. 3. Quantitation of specific antibodies by enzyme-labeled anti-immunoglobulin in antigen-coated tubes. J Immunol. 1972 Jul;109(1):129–135. [PubMed] [Google Scholar]
  11. Estess P., Lamoyi E., Nisonoff A., Capra J. D. Structural studies on induced antibodies with defined idiotypic specificities. IX. Framework differences in the heavy- and light-chain-variable regions of monoclonal anti-p-azophenylarsonate antibodies from A/J mice differing with respect to a cross-reactive idiotype. J Exp Med. 1980 Apr 1;151(4):863–875. doi: 10.1084/jem.151.4.863. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. 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]
  13. Goodman J. W., Lewis G. K., Primi D., Hornbeck P., Ruddle N. H. Antigen-specific molecules from murine T lymphocytes and T cell hybridomas. Mol Immunol. 1980 Jul;17(7):933–945. doi: 10.1016/0161-5890(80)90042-5. [DOI] [PubMed] [Google Scholar]
  14. Huchet R., Feldmann M. Studies on antibody affinity in mice. Eur J Immunol. 1973 Jan;3(1):49–55. doi: 10.1002/eji.1830030111. [DOI] [PubMed] [Google Scholar]
  15. Imanishi-Kari T., Rajnavölgyi E., Takemori T., Jack R. S., Rajewsky K. The effect of light chain gene expression on the inheritance of an idiotype associated with primary anti-(4-hydroxy-3-nitrophenyl)acetyl(NP) antibodies. Eur J Immunol. 1979 Apr;9(4):324–331. doi: 10.1002/eji.1830090414. [DOI] [PubMed] [Google Scholar]
  16. Jack R. S., Imanishi-Kari T., Rajewsky K. Idiotypic analysis of the response of C57BL/6 mice to the (4-hydroxy-3-nitrophenyl)acetyl group. Eur J Immunol. 1977 Aug;7(8):559–565. doi: 10.1002/eji.1830070813. [DOI] [PubMed] [Google Scholar]
  17. Jerne N. K., Henry C., Nordin A. A., Fuji H., Koros A. M., Lefkovits I. Plaque forming cells: methodology and theory. Transplant Rev. 1974;18:130–191. doi: 10.1111/j.1600-065x.1974.tb01588.x. [DOI] [PubMed] [Google Scholar]
  18. Ju S., Gray A., Nisonoff A. Frequency of occurrence of idiotypes associated with anti-p-azophenylarsonate antibodies arising in mice immunologically suppressed with respect to a cross-reactive idiotype. J Exp Med. 1977 Mar 1;145(3):540–556. doi: 10.1084/jem.145.3.540. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Kapsalis A. A., Tung A. S., Nisonoff A. Relative combining affinities of anti-p-azophenylarsonate antibodies bearing a cross-reactive idiotype. Immunochemistry. 1976 Sep;13(9):783–787. doi: 10.1016/0019-2791(76)90201-9. [DOI] [PubMed] [Google Scholar]
  20. Karjalainen K. Two major idiotypes in mouse anti-(4-hydroxy-3-nitro-phenyl)acetyl (NP) antibodies are controlled by "allelic" genes. Eur J Immunol. 1980 Feb;10(2):132–139. doi: 10.1002/eji.1830100212. [DOI] [PubMed] [Google Scholar]
  21. Kelsoe G., Isaak D., Cerny J. Thymic requirement for cyclical idiotypic and reciprocal anti-idiotypic immune responses to a T-independent antigen. J Exp Med. 1980 Feb 1;151(2):289–300. doi: 10.1084/jem.151.2.289. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Kuettner M. G., Wang A. L., Nisonoff A. Quantitative investigations of idiotypic antibodies. VI. Idiotypic specificity as a potential genetic marker for the variable regions of mouse immunoglobulin polypeptide chains. J Exp Med. 1972 Mar 1;135(3):579–595. doi: 10.1084/jem.135.3.579. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Lamoyi E., Estess P., Capra J. D., Nisonoff A. Heterogeneity of an intrastrain cross-reactive idiotype associated with anti-p-azophenylarsonate antibodies of A/J mice. J Immunol. 1980 Jun;124(6):2834–2840. [PubMed] [Google Scholar]
  24. Laskin J. A., Gray A., Nisonoff A., Klinman N. R., Gottlieb P. D. Segregation at a locus determining an immunoglobulin genetic marker for the light chain variable region affects inheritance of expression of an idiotype. Proc Natl Acad Sci U S A. 1977 Oct;74(10):4600–4604. doi: 10.1073/pnas.74.10.4600. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Lewis G. K., Ranken R., Nitecki D. E., Goodman J. W. Murine B-cell subpopulations responsive to T-dependent and T-independent antigens. J Exp Med. 1976 Aug 1;144(2):382–397. doi: 10.1084/jem.144.2.382. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Lieberman R., Bona C., Chien C. C., Stein K. E., Paul W. E. Genetic and cellular regulation of the expression of specific antibody idiotypes in the anti-polyfructosan immune response. Ann Immunol (Paris) 1979 Mar-Apr;130(2):247–262. [PubMed] [Google Scholar]
  27. 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]
  28. Marshak-Rothstein A., Benedetto J. D., Kirsch R. L., Gefter M. L. Unique determinants associated with hybridoma proteins expressing a cross-reactive idiotype: frequency among individual immune sera. J Immunol. 1980 Nov;125(5):1987–1992. [PubMed] [Google Scholar]
  29. Marshak-Rothstein A., Siekevitz M., Margolies M. N., Mudgett-Hunter M., Gefter M. L. Hybridoma proteins expressing the predominant idiotype of the antiazophenylarsonate response of A/J mice. Proc Natl Acad Sci U S A. 1980 Feb;77(2):1120–1124. doi: 10.1073/pnas.77.2.1120. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Mitchell G. F. T cell modification of B cell responses to antigen in mice. Contemp Top Immunobiol. 1974;3:97–116. doi: 10.1007/978-1-4684-3045-5_4. [DOI] [PubMed] [Google Scholar]
  31. Mäkelä O., Karjalainen K. Inheritance of antibody specificity. IV. Control of related molecular species by one VH gene. Cold Spring Harb Symp Quant Biol. 1977;41(Pt 2):735–741. doi: 10.1101/sqb.1977.041.01.084. [DOI] [PubMed] [Google Scholar]
  32. Mäkelä O., Karjalainen K. Inherited immunoglobulin idiotypes of the mouse. Immunol Rev. 1977;34:119–138. doi: 10.1111/j.1600-065x.1977.tb00370.x. [DOI] [PubMed] [Google Scholar]
  33. Mäkelä O., Karjalainen K., Ju S. T., Nisonoff A. Two str1cturally similar haptens each induce a different inherited idiotype. Eur J Immunol. 1977 Dec;7(12):831–835. doi: 10.1002/eji.1830071202. [DOI] [PubMed] [Google Scholar]
  34. 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]
  35. Pawlak L. L., Mushinski E. B., Nisonoff A., Potter M. Evidence for the linkage of the IGC H locus to a gene controlling the idiotypic specificity of anti-p-azophenylarsonate antibodies in strain A mice. J Exp Med. 1973 Jan 1;137(1):22–31. doi: 10.1084/jem.137.1.22. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Stein K. E., Bona C., Lieberman R., Chien C. C., Paul W. E. Regulation of the anti-inulin antibody response by a nonallotype-linked gene. J Exp Med. 1980 May 1;151(5):1088–1102. doi: 10.1084/jem.151.5.1088. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. TABACHNICK M., SOBOTKA H. Azoproteins. II. A spectrophotometric study of the coupling of diazotized arsanilic acid with proteins. J Biol Chem. 1960 Apr;235:1051–1054. [PubMed] [Google Scholar]
  38. Wabl M. R., Forni L., Loor F. Switch in immunoglobulin class production observed in single clones of committed lymphocytes. Science. 1978 Mar 10;199(4333):1078–1080. doi: 10.1126/science.305113. [DOI] [PubMed] [Google Scholar]
  39. 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