Skip to main content
NCBI home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1983 Dec 1;158(6):1868–1880. doi: 10.1084/jem.158.6.1868

Tolerance for self IG at the level of the Ly1+ T cell

PMCID: PMC2187155  PMID: 6417259

Abstract

Experiments presented in this report demonstrate that specificity of the Ly1+ T cell proliferative response to NP-modified Ig is controlled by Igh-C-linked genes. In addition, we describe the mechanism whereby Igh-C-encoded molecules influence Ly1+ T cell activity. We show that Igh-C-linked control of T cell responses to NP-modified Ig is a secondary consequence of naturally acquired tolerance for self Ig. Unresponsiveness to self Ig is not due to a defect expressed functionally at the level of the antigen-presenting cell, nor is it associated with active suppression. These results suggest that tolerance for self Ig at the level of the Ly1+ T cell is due to functional deletion of Ly1+ T cell clones specific for self Ig. The possibility is considered that regulatory effects mediated by passively administered antibodies may in part be due to induction of Ly1+ T cell tolerance for self Ig.

Full Text

The Full Text of this article is available as a PDF (923.5 KB).

Selected References

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

  1. Benjamin D. C. Neonatally induced tolerance to HGG: duration in B cells and absence of specific suppressor cells. J Immunol. 1977 Jul;119(1):311–314. [PubMed] [Google Scholar]
  2. Bikoff E., Bona C. A. Influence of Igh-C- and MHC-linked genes on the activity of immunoglobulin-recognizing T cells. J Immunol. 1983 Jul;131(1):103–108. [PubMed] [Google Scholar]
  3. Bikoff E. T-cell proliferative response to hapten-modified self-immunoglobulins: recognition of conjugate-specific determinants. Proc Natl Acad Sci U S A. 1982 Jul;79(13):4156–4160. doi: 10.1073/pnas.79.13.4156. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bona C. A., Heber-Katz E., Paul W. E. Idiotype-anti-idiotype regulation. I. Immunization with a levan-binding myeloma protein leads to the appearance of auto-anti-(anti-idiotype) antibodies and to the activation of silent clones. J Exp Med. 1981 Apr 1;153(4):951–967. doi: 10.1084/jem.153.4.951. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bona C., Paul W. E. Cellular basis of regulation of expression of idiotype. I. T-suppressor cells specific for MOPC 460 idiotype regulate the expression of cells secreting anti-TNP antibodies bearing 460 idiotype. J Exp Med. 1979 Mar 1;149(3):592–600. doi: 10.1084/jem.149.3.592. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bottomly K., Janeway C. A., Jr, Mathieson B. J., Mosier D. E. Absence of an antigen-specific helper T cell required for the expression of the T 15 idiotype in mice treated with anti-mu antibody. Eur J Immunol. 1980 Feb;10(2):159–163. doi: 10.1002/eji.1830100217. [DOI] [PubMed] [Google Scholar]
  7. 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]
  8. Chen S. S., Katz D. H. IgE class-restricted tolerance induced by neonatal administration of soluble or cell-bound IgE. J Exp Med. 1983 Feb 1;157(2):772–788. doi: 10.1084/jem.157.2.772. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Corradin G., Etlinger H. M., Chiller J. M. Lymphocyte specificity to protein antigens. I. Characterization of the antigen-induced in vitro T cell-dependent proliferative response with lymph node cells from primed mice. J Immunol. 1977 Sep;119(3):1048–1053. [PubMed] [Google Scholar]
  10. 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]
  11. Doyle M. V., Parks D. E., Weigle W. O. Specific suppression of the immune response by HGG tolerant spleen cells. I. Parameters affecting the level of suppression. J Immunol. 1976 Jun;116(6):1640–1645. [PubMed] [Google Scholar]
  12. Eardley D. D., Shen F. W., Cantor H., Gershon R. K. Genetic control of immunoregulatory circuits. Genes linked to the Ig locus govern communication between regulatory T-cell sets. J Exp Med. 1979 Jul 1;150(1):44–50. doi: 10.1084/jem.150.1.44. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. 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]
  14. Ey P. L., Prowse S. J., Jenkin C. R. Isolation of pure IgG1, IgG2a and IgG2b immunoglobulins from mouse serum using protein A-sepharose. Immunochemistry. 1978 Jul;15(7):429–436. doi: 10.1016/0161-5890(78)90070-6. [DOI] [PubMed] [Google Scholar]
  15. Gleason K., Pierce S., Köhler H. Generation of idiotype-specific T cell help through network perturbation. J Exp Med. 1981 Apr 1;153(4):924–935. doi: 10.1084/jem.153.4.924. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Herzenberg L. A., Okumura K., Cantor H., Sato V. L., Shen F. W., Boyse E. A., Herzenberg L. A. T-cell regulation of antibody responses: demonstration of allotype-specific helper T cells and their specific removal by suppressor T cells. J Exp Med. 1976 Aug 1;144(2):330–344. doi: 10.1084/jem.144.2.330. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Hetzelberger D., Eichmann K. Recognition of idiotypes in lymphocyte interactions. I. Idiotypic selectivity in the cooperation between T and B lymphocytes. Eur J Immunol. 1978 Dec;8(12):846–852. doi: 10.1002/eji.1830081205. [DOI] [PubMed] [Google Scholar]
  18. Iverson G. M. Ability of CBA mice to produce anti-idiotypic sera to 5563 myeloma protein. Nature. 1970 Jul 18;227(5255):273–274. doi: 10.1038/227273a0. [DOI] [PubMed] [Google Scholar]
  19. Iverson G. M., Eardley D. D., Janeway C. A., Gershon R. K. Use of anti-idiotype immunosorbents to isolate circulating antigen-specific T cell-derived molecules from hyperimmune sera. Proc Natl Acad Sci U S A. 1983 Mar;80(5):1435–1439. doi: 10.1073/pnas.80.5.1435. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Janeway C. A., Jr, Murgita R. A., Weinbaum F. I., Asofsky R., Wigzell H. Evidence for an immunoglobulin-dependent antigen-specific helper T cell. Proc Natl Acad Sci U S A. 1977 Oct;74(10):4582–4586. doi: 10.1073/pnas.74.10.4582. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Jerne N. K. Towards a network theory of the immune system. Ann Immunol (Paris) 1974 Jan;125C(1-2):373–389. [PubMed] [Google Scholar]
  22. Julius M. H., Simpson E., Herzenberg L. A. A rapid method for the isolation of functional thymus-derived murine lymphocytes. Eur J Immunol. 1973 Oct;3(10):645–649. doi: 10.1002/eji.1830031011. [DOI] [PubMed] [Google Scholar]
  23. Juy D., Primi D., Sanchez P., Cazenave P. A. Idiotype regulation: evidence for the involvement of Igh-C-restricted T cells in the M-460 idiotype suppressive pathway. Eur J Immunol. 1982 Jan;12(1):24–30. doi: 10.1002/eji.1830120107. [DOI] [PubMed] [Google Scholar]
  24. Kahan B., Auerbach R., Alter B. J., Bach F. H. Histocompatibility and isoenzyme differences in commercially supplied "BALB/c" mice. Science. 1982 Jul 23;217(4557):379–381. doi: 10.1126/science.6953593. [DOI] [PubMed] [Google Scholar]
  25. Kemp D. J., Adams J. M., Mottram P. L., Thomas W. R., Walker I. D., Miller J. F. A search for messenger RNA molecules bearing immunoglobulin VH nucleotide sequences in T cells. J Exp Med. 1982 Dec 1;156(6):1848–1853. doi: 10.1084/jem.156.6.1848. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. 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]
  27. 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]
  28. Kresina T. F., Nisonoff A. Passive transfer of the idiotypically suppressed state by serum from suppressed mice and transfer of suppression from mothers to offspring. J Exp Med. 1983 Jan 1;157(1):15–23. doi: 10.1084/jem.157.1.15. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Kronenberg M., Davis M. M., Early P. W., Hood L. E., Watson J. D. Helper and killer T cells do not express B cell immunoglobulin joining and constant region gene segments. J Exp Med. 1980 Dec 1;152(6):1745–1761. doi: 10.1084/jem.152.6.1745. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Kurosawa Y., von Boehmer H., Haas W., Sakano H., Trauneker A., Tonegawa S. Identification of D segments of immunoglobulin heavy-chain genes and their rearrangement in T lymphocytes. Nature. 1981 Apr 16;290(5807):565–570. doi: 10.1038/290565a0. [DOI] [PubMed] [Google Scholar]
  31. L'Age-Stehr J. Priming of T helper cells by antigen-activated B cells. B cell-primed Lyt-1+ helper cells are restricted to cooperate with B cells expressing the IgvH phenotype of the priming B cells. J Exp Med. 1981 May 1;153(5):1236–1245. doi: 10.1084/jem.153.5.1236. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Lamb J. R., Skidmore B. J., Green N., Chiller J. M., Feldmann M. Induction of tolerance in influenza virus-immune T lymphocyte clones with synthetic peptides of influenza hemagglutinin. J Exp Med. 1983 May 1;157(5):1434–1447. doi: 10.1084/jem.157.5.1434. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. 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]
  34. Mongini P. K., Paul W. E. T cell regulation of the IgG2a response to TNP-Ficoll: evidence that allotype congenic mice contain both helper cells that preferentially enhance IgG2a synthesis and suppressor cells that specifically suppress IgG2 synthesis. J Immunol. 1982 Jun;128(6):2405–2410. [PubMed] [Google Scholar]
  35. Nutt N., Haber J., Wortis H. H. Influence of Igh-linked gene products on the generation of T helper cells in the response to sheep erythrocytes. J Exp Med. 1981 May 1;153(5):1225–1235. doi: 10.1084/jem.153.5.1225. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Ortiz-Ortiz L., Weigle W. O., Parks D. E. Deregulation of idiotype expression. Induction of tolerance in an anti-idiotypic response. J Exp Med. 1982 Sep 1;156(3):898–911. doi: 10.1084/jem.156.3.898. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. 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]
  38. Owen F. L., Riblet R., Gottlieb P. D. T suppressor cells activated by anti-Tsud serum are Igh-V-restricted. Eur J Immunol. 1982 Jan;12(1):94–97. doi: 10.1002/eji.1830120118. [DOI] [PubMed] [Google Scholar]
  39. Owen F. L., Riblet R., Taylor B. A. The T suppressor cell alloantigen Tsud maps near immunoglobulin allotype genes and may be an heavy chain constant-region marker on a T cell receptor. J Exp Med. 1981 Apr 1;153(4):801–810. doi: 10.1084/jem.153.4.801. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Owen F. L., Spurll G. M., Panageas E. Tthyd, a new thymocyte alloantigen linked to Igh-1. Implications for a switch mechanism for T cell antigen receptors. J Exp Med. 1982 Jan 1;155(1):52–60. doi: 10.1084/jem.155.1.52. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Parks D. E., Doyle M. V., Weigle W. O. Induction and mode of action of suppressor cells generated against human gamma globulin. I. An immunologic unresponsive state devoid of demonstrable suppressor cells. J Exp Med. 1978 Sep 1;148(3):625–638. doi: 10.1084/jem.148.3.625. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. 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]
  43. Rosenberg Y. J., Asofsky R. T cell regulation of isotype expression. The requirement for a second Ig-specific helper T cell population for the induction of IgG responses. Eur J Immunol. 1981 Sep;11(9):705–710. doi: 10.1002/eji.1830110907. [DOI] [PubMed] [Google Scholar]
  44. Rosenberg Y. J. Isotype-specific T cell regulation of immunoglobulin expression. Immunol Rev. 1982;67:33–58. doi: 10.1111/j.1600-065x.1982.tb01054.x. [DOI] [PubMed] [Google Scholar]
  45. Rubinstein L. J., Yeh M., Bona C. A. Idiotype-anti-idiotype network. II. Activation of silent clones by treatment at birth with idiotypes is associated with the expansion of idiotype-specific helper T cells. J Exp Med. 1982 Aug 1;156(2):506–521. doi: 10.1084/jem.156.2.506. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Segal S., Tzehoval E., Feldman M. Immunological tolerance: high-dose antigen-induced suppressor cells from tolerant animals inactivate antigen-presenting macrophages. Proc Natl Acad Sci U S A. 1979 May;76(5):2405–2409. doi: 10.1073/pnas.76.5.2405. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Spurll G. M., Owen F. L. A family of T-cell alloantigens linked to Igh-1. Nature. 1981 Oct 29;293(5835):742–745. doi: 10.1038/293742a0. [DOI] [PubMed] [Google Scholar]
  48. Sy M. S., Bach B. A., Dohi Y., Nisonoff A., Benacerraf B., Greene M. I. Antigen- and receptor-driven regulatory mechanisms. I. Induction of suppressor T cells with anti-idiotypic antibodies. J Exp Med. 1979 Nov 1;150(5):1216–1228. doi: 10.1084/jem.150.5.1216. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Waters C. A., Pilarski L. M., Wegmann T. G., Diener E. Tolerance induction during ontogeny. I. Presence of active suppression in mice rendered tolerant to human gamma-globulin in utero correlates with the breakdown of the tolerant state. J Exp Med. 1979 May 1;149(5):1134–1151. doi: 10.1084/jem.149.5.1134. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Weinberger J. Z., Benacerraf B., Dorf M. E. Hapten-specific T cell responses to 4-hydroxy-3-nitrophenyl acetyl. III. Interaction of effector suppressor T cells is restricted by H-2 and Igh-V genes. J Exp Med. 1980 Jun 1;151(6):1413–1423. doi: 10.1084/jem.151.6.1413. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. 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