Abstract
A/He mice actively producing complementary or anti-idiotypic antibody directed against a combining site structure for phosphorylcholine (PC) have profound and long-lasting suppression of their response to PC. B cells from unresponsive mice are unresponsive in vitro, and attempts to demonstrate suppressor cells in unresponsive mice were unsuccessful. Although the process ultimately responsible for suppression has not been defined, suppression can be initiated by anti-idiotypic antibody alone and prevented by complementary Ig; i.e., by anti-PC antibody. Furthermore, a suppressed anti-PC response can be rescued by sublethal irradiation and anti-PC antibody given passively. The recovery of the suppressed response is slow and presumably results from maturation from "stem" cells, which are protected from tolerization by the passively given antibody. Thus, by extrapolation, one of the functions of secreted Ig may be to protect the clone that produces it.
Full Text
The Full Text of this article is available as a PDF (974.1 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Abbas A. K., Perry L. L., Bach B. A., Greene M. I. Idiotype-specific T cell immunity. I. Generation of effector and suppressor T lymphocytes reactive with myeloma idiotypic determinants. J Immunol. 1980 Mar;124(3):1160–1166. [PubMed] [Google Scholar]
- Adorini L., Harvey M., Sercarz E. E. The fine specificity of regulatory T cells. IV. Idiotypic complementarity and antigen-bridging interactions in the anti-lysozyme response. Eur J Immunol. 1979 Nov;9(11):906–909. doi: 10.1002/eji.1830091113. [DOI] [PubMed] [Google Scholar]
- Anderson R. E., Warner N. L. Ionizing radiation and the immune response. Adv Immunol. 1976;24:215–335. doi: 10.1016/s0065-2776(08)60331-4. [DOI] [PubMed] [Google Scholar]
- Benca R., Quintáns J., Kearney J. F., Flood P. M., Schreiber H. Studies on phosphorylcholine-specific T cell idiotypes and idiotype-specific immunity. Mol Immunol. 1980 Jul;17(7):823–831. doi: 10.1016/0161-5890(80)90031-0. [DOI] [PubMed] [Google Scholar]
- 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]
- Bona C., Hooghe R., Cazenave P. A., Leguérn C., Paul W. E. Cellular basis of regulation of expression of idiotype. II. Immunity to anti-MOPC-460 idiotype antibodies increases the level of anti-trinitrophenyl antibodies bearing 460 idiotypes. J Exp Med. 1979 Apr 1;149(4):815–823. doi: 10.1084/jem.149.4.815. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bona C., Lieberman R., Chien C. C., Mond J., House S., Green I., Paul W. E. Immune response to levan. I. Kinetics and ontogeny of anti-levan and anti-inulin antibody response and of expression of cross-reactive idiotype. J Immunol. 1978 Apr;120(4):1436–1442. [PubMed] [Google Scholar]
- 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]
- 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]
- 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]
- Cambier J. C., Vitetta E. S., Uhr J. W., Kettman J. R. B-cell tolerance. II. Trinitrophenyl human gamma globulin-induced tolerance in adult and neonatal murine B cells responsive to thymus-dependent and independent forms of the same hapten. J Exp Med. 1977 Mar 1;145(3):778–783. doi: 10.1084/jem.145.3.778. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cazenave P. A. Idiotypic-anti-idiotypic regulation of antibody synthesis in rabbits. Proc Natl Acad Sci U S A. 1977 Nov;74(11):5122–5125. doi: 10.1073/pnas.74.11.5122. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cosenza H., Köhler H. Specific suppression of the antibody response by antibodies to receptors. Proc Natl Acad Sci U S A. 1972 Sep;69(9):2701–2705. doi: 10.1073/pnas.69.9.2701. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dohi Y., Nisonoff A. Suppression of idiotype and generation of suppressor T cells with idiotype-conjugated thymocytes. J Exp Med. 1979 Oct 1;150(4):909–918. doi: 10.1084/jem.150.4.909. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Eichmann K. Expression and function of idiotypes of lymphocytes. Adv Immunol. 1978;26:195–254. doi: 10.1016/s0065-2776(08)60231-x. [DOI] [PubMed] [Google Scholar]
- Eichmann K., Falk I., Rajewsky K. Recognition of idiotypes in lymphocyte interactions. II. Antigen-independent cooperation between T and B lymphocytes that possess similar and complementary idiotypes. Eur J Immunol. 1978 Dec;8(12):853–857. doi: 10.1002/eji.1830081206. [DOI] [PubMed] [Google Scholar]
- 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]
- 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]
- Eig B. M., Ju S. T., Nisonoff A. Complete inhibition of the expression of an idiotype by a mechanism of B-cell dominance. J Exp Med. 1977 Dec 1;146(6):1574–1584. doi: 10.1084/jem.146.6.1574. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fernandez C., Möller G. Antigen-induced strain-specific autoantiidiotypic antibodies modulate the immune response to dextran B 512. Proc Natl Acad Sci U S A. 1979 Nov;76(11):5944–5947. doi: 10.1073/pnas.76.11.5944. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Flood P. M., Kripke M. L., Rowley D. A., Schreiber H. Suppression of tumor rejection by autologous anti-idiotypic immunity. Proc Natl Acad Sci U S A. 1980 Apr;77(4):2209–2213. doi: 10.1073/pnas.77.4.2209. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Jerne N. K. Towards a network theory of the immune system. Ann Immunol (Paris) 1974 Jan;125C(1-2):373–389. [PubMed] [Google Scholar]
- 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]
- Kaplan D. R., Quintans J., Köhler H. Clonal dominance: loss and restoration in adoptive transfer. Proc Natl Acad Sci U S A. 1978 Apr;75(4):1967–1970. doi: 10.1073/pnas.75.4.1967. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kay T. W., Pike B. L., Nossal G. J. Mechanisms of clonal abortion tolerogenesis. IV. Verification of the hypothesis in living mice. J Immunol. 1980 Apr;124(4):1579–1584. [PubMed] [Google Scholar]
- Kelsoe G., Cerny J. Reciprocal expansions of idiotypic and anti-idiotypic clones following antigen stimulation. Nature. 1979 May 24;279(5711):333–334. doi: 10.1038/279333a0. [DOI] [PubMed] [Google Scholar]
- 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]
- Kim B. S. Mechanisms of idiotype suppression. II. Requirement of specific antigen for B cell inactivation by anti-idiotype antibody. J Immunol. 1979 Dec;123(6):2499–2504. [PubMed] [Google Scholar]
- McKearn J. P., Quintáns J. Delineation of tolerance-sensitive and tolerance-insensitive B cells in normal and immune defective mice. J Immunol. 1980 Jan;124(1):77–80. [PubMed] [Google Scholar]
- McKearn J. P., Quintáns J. Idiotype-specific tolerance: preferential alteration of idiotype expression after neonatal exposure to tolerogen. J Immunol. 1980 Apr;124(4):1983–1989. [PubMed] [Google Scholar]
- McKearn T. J., Hamada Y., Stuart F. P., Fitch F. W. Anti-receptor antibody and resistance to graft-versus-host disease. Nature. 1974 Oct 18;251(5476):648–650. doi: 10.1038/251648a0. [DOI] [PubMed] [Google Scholar]
- Metcalf E. S., Klinman N. R. In vitro tolerance induction of neonatal murine B cells. J Exp Med. 1976 Jun 1;143(6):1327–1340. doi: 10.1084/jem.143.6.1327. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Metcalf E. S., Scher I., Klinman N. R. Susceptibility to in vitro tolerance induction of adult B cells from mice with an X-linked B-cell defect. J Exp Med. 1980 Feb 1;151(2):486–491. doi: 10.1084/jem.151.2.486. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nossal G. J., Pike B. L. Evidence for the clonal abortion theory of B-lymphocyte tolerance. J Exp Med. 1975 Apr 1;141(4):904–917. [PMC free article] [PubMed] [Google Scholar]
- Nossal G. J., Pike B. L. Mechanisms of clonal abortion tolerogenesis. I. Response of immature hapten-specific B lymphocytes. J Exp Med. 1978 Nov 1;148(5):1161–1170. doi: 10.1084/jem.148.5.1161. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Owen F. L., Nisonoff A. Effect of idiotype-specific suppressor T cells on primary and secondary responses. J Exp Med. 1978 Jul 1;148(1):182–194. doi: 10.1084/jem.148.1.182. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- 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]
- 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]
- Rowley D. A., Köhler H., Cowan J. D. An immunologic network. Contemp Top Immunobiol. 1980;9:205–230. doi: 10.1007/978-1-4615-9131-3_8. [DOI] [PubMed] [Google Scholar]
- 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]
- Rowley D. A., Miller G. W., Lorbach I. Simultaneous complementary idiotypic responses: absence of reciprocal regulation. J Exp Med. 1978 Jul 1;148(1):148–162. doi: 10.1084/jem.148.1.148. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sakato N., Hall S. H., Eisen H. N. Restricted heterogeneity of antibodies to idiotypes of isologous immunoglobulins. Immunochemistry. 1977 Aug;14(8):621–625. doi: 10.1016/0019-2791(77)90159-8. [DOI] [PubMed] [Google Scholar]
- 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]
- 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. III. Absence in nu/nu mice: evidence for T-cell dependence of the anti-idiotypic-antibody response. J Exp Med. 1979 Oct 1;150(4):808–817. doi: 10.1084/jem.150.4.808. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Strayer D. S., Cosenza H., Lee W. M., Rowley D. A., Köhler H. Neonatal tolerance induced by antibody against antigen-specific receptor. Science. 1974 Nov 15;186(4164):640–643. doi: 10.1126/science.186.4164.640. [DOI] [PubMed] [Google Scholar]
- Sy M. S., Moorhead J. W., Claman H. N. Regulation of cell mediated immunity by antibodies: possible role of anti-receptor antibodies in the regulation of contact sensitivity to DNFB in mice. J Immunol. 1979 Dec;123(6):2593–2598. [PubMed] [Google Scholar]
- Teale J. M., Mandel T. E. Ontogenic development of B-lymphocyte function and tolerance susceptibility in vivo and in an in vitro organ culture system. J Exp Med. 1980 Feb 1;151(2):429–445. doi: 10.1084/jem.151.2.429. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ward K., Cantor H., Nisonoff A. Analysis of the cellular basis of idiotype-specific suppression. J Immunol. 1978 Jun;120(6):2016–2019. [PubMed] [Google Scholar]
- 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]
- Yamamoto H., Nonaka M., Katz D. H. Suppression of hapten-specific delayed-type hypersensitivity responses in mice by idiotype-specific suppressor T cells after administration of anti-idiotypic antibodies. J Exp Med. 1979 Oct 1;150(4):818–829. doi: 10.1084/jem.150.4.818. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zubler R. H., Benacerraf B., Germain R. N. Feedback suppression of the immune response in vitro. II. IgVH-restricted antibody-dependent suppression. J Exp Med. 1980 Mar 1;151(3):681–694. doi: 10.1084/jem.151.3.681. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zubler R. H., Cantor H., Benacerraf B., Germain R. N. Feedback suppression of the immune response in vitro. I. Activity of antigen-stimulated B cells. J Exp Med. 1980 Mar 1;151(3):667–680. doi: 10.1084/jem.151.3.667. [DOI] [PMC free article] [PubMed] [Google Scholar]