Abstract
Extensive idiotypic connectivity has been discovered between the antibodies composing the immune responses against the acetylcholine receptor (AChR) and alpha-1,3-dextran. The idiotypic connections form an elaborate network linking these disparate antigen systems, and there is an hierarchical organization of the antibodies in this network. The key anti-Ids that interconnect these two responses are more crossreactive, lower-affinity antibodies. Interestingly, 15% of patients with MG, which is caused by autoantibodies against the AChR, have serum antibodies against DEX. Control sera are negative for anti- DEX antibodies. Certain anti-DEX antibodies also bind to anti-AChR antibodies via idiotypic interactions. These findings suggest a model for the initiation of autoimmunity in MG. Antibodies made in response to DEX epitopes on the surface of certain bacteria would elicit the production of anti-Ids. However, some of these anti-Ids would also be autoantibodies against the AChR. Thus, is some circumstances, autoimmunity may develop as a consequence of the normal operation of regulatory idiotypic networks.
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Selected References
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- Bona C. A., Finley S., Waters S., Kunkel H. G. Anti-immunoglobulin antibodies. III. Properties of sequential anti-idiotypic antibodies to heterologous anti-gamma globulins. Detection of reactivity of anti-idiotype antibodies with epitopes of Fc fragments (homobodies) and with epitopes and idiotopes (epibodies). J Exp Med. 1982 Oct 1;156(4):986–999. doi: 10.1084/jem.156.4.986. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dwyer D. S., Bradley R. J., Urquhart C. K., Kearney J. F. An enzyme-linked immunoabsorbent assay for measuring antibodies against muscle acetylcholine receptor. J Immunol Methods. 1983 Feb 25;57(1-3):111–119. doi: 10.1016/0022-1759(83)90069-8. [DOI] [PubMed] [Google Scholar]
- Dwyer D. S., Bradley R. J., Urquhart C. K., Kearney J. F. Naturally occurring anti-idiotypic antibodies in myasthenia gravis patients. Nature. 1983 Feb 17;301(5901):611–614. doi: 10.1038/301611a0. [DOI] [PubMed] [Google Scholar]
- Dwyer D. S., Kearney J. F., Bradley R. J., Kemp G. E., Oh S. J. Interaction of human antibody and murine monoclonal antibody with muscle acetylcholine receptor. Ann N Y Acad Sci. 1981;377:143–157. doi: 10.1111/j.1749-6632.1981.tb33729.x. [DOI] [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]
- Hiernaux J., Bona C. A. Shared idiotypes among monoclonal antibodies specific for different immunodominant sugars of lipopolysaccharide of different Gram-negative bacteria. Proc Natl Acad Sci U S A. 1982 Mar;79(5):1616–1620. doi: 10.1073/pnas.79.5.1616. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Holmberg D., Forsgren S., Ivars F., Coutinho A. Reactions among IgM antibodies derived from normal, neonatal mice. Eur J Immunol. 1984 May;14(5):435–441. doi: 10.1002/eji.1830140510. [DOI] [PubMed] [Google Scholar]
- Hornbeck P. V., Lewis G. K. Idiotype connectance in the immune system. II. A heavy chain variable region idiotope that dominates the antibody response to the p-azobenzenearsonate group is a minor idiotope in the response to trinitrophenyl group. J Exp Med. 1985 Jan 1;161(1):53–71. doi: 10.1084/jem.161.1.53. [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]
- Kearney J. F., Barletta R., Quan Z. S., Quintáns J. Monoclonal vs. heterogeneous anti-H-8 antibodies in the analysis of the anti-phosphorylcholine response in BALB/c mice. Eur J Immunol. 1981 Nov;11(11):877–883. doi: 10.1002/eji.1830111106. [DOI] [PubMed] [Google Scholar]
- Kearney J. F., McCarthy M. T., Stohrer R., Benjamin W. H., Jr, Briles D. E. Induction of germ-line anti-alpha 1-3 dextran antibody responses in mice by members of the Enterobacteriaceae family. J Immunol. 1985 Nov;135(5):3468–3472. [PubMed] [Google Scholar]
- Lindstrom J., Dau P. Biology of myasthenia gravis. Annu Rev Pharmacol Toxicol. 1980;20:337–362. doi: 10.1146/annurev.pa.20.040180.002005. [DOI] [PubMed] [Google Scholar]
- Metzger D. W., Miller A., Sercarz E. E. Sharing of an idiotypic marker by monoclonal antibodies specific for distinct regions of hen lysozyme. Nature. 1980 Oct 9;287(5782):540–542. doi: 10.1038/287540a0. [DOI] [PubMed] [Google Scholar]
- Plotz P. H. Autoantibodies are anti-idiotype antibodies to antiviral antibodies. Lancet. 1983 Oct 8;2(8354):824–826. doi: 10.1016/s0140-6736(83)90740-7. [DOI] [PubMed] [Google Scholar]
- Rajewsky K., Takemori T. Genetics, expression, and function of idiotypes. Annu Rev Immunol. 1983;1:569–607. doi: 10.1146/annurev.iy.01.040183.003033. [DOI] [PubMed] [Google Scholar]
- Stohrer R., Kearney J. Ontogeny of B cell precursors responding to alpha 1- greater than 3 dextran in BALB/c mice. J Immunol. 1984 Nov;133(5):2323–2326. [PubMed] [Google Scholar]
- Victor-Kobrin C., Manser T., Moran T. M., Imanishi-Kari T., Gefter M., Bona C. A. Shared idiotopes among antibodies encoded by heavy-chain variable region (VH) gene members of the J558 VH family as basis for cross-reactive regulation of clones with different antigen specificity. Proc Natl Acad Sci U S A. 1985 Nov;82(22):7696–7700. doi: 10.1073/pnas.82.22.7696. [DOI] [PMC free article] [PubMed] [Google Scholar]