{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T21:35:37Z","timestamp":1790804137350,"version":"4.1.0"},"reference-count":82,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T00:00:00Z","timestamp":1763337600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Seminal discoveries led to the concept of the immune system as a complex network of antibodies and B-cells. In 1963, Kunkel et\u00a0al. described individual antigenic specificities using antibodies directed against antibodies, hinting at the possibility of a network structure in the immune repertoire. In 1973, Jerne proposed the Network Theory that the immune system is a functional network of antibodies (idiotypes) and anti-idiotypic antibodies that are made in response due to the inherent immunogenicity of immunoglobulin variable chains. In 1974, anti-idiotypic responses were observed, providing proof of the Network Theory. In this review, the origin, as well as rise and fall, of idiotype research over the years is traced, citing examples of work that expanded the understanding of the network concept and its potential application. This includes broadly binding anti-idiotypic antibodies, anti-idiotype vaccines, anti-idiotypic antibodies as tools to trace monoclonal antibodies, and as immunotherapeutic biologicals. Future utility from using the Network Theory could involve cocktails of different monoclonal anti-idiotypic monoclonals. Studies can focus on how the Network Theory involves the generation of potential \u201cantigen mirror\u201d effects and how the network ultimately regulates both B and T cell responses over time. Despite the decline in popularity, aspects of the Network Theory are reemerging as evidence is generated on potential roles during host responses to pathogens or vaccines.<\/jats:p>","DOI":"10.3389\/fimmu.2025.1686107","type":"journal-article","created":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T05:17:20Z","timestamp":1763356640000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["The past, present, and future of anti-idiotype antibodies"],"prefix":"10.3389","volume":"16","author":[{"given":"William J.","family":"Murphy","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig P.","family":"Collins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heinz","family":"Kohler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,11,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.00808","article-title":"The promise of anti-idiotype revisited","volume":"10","author":"Kohler","year":"2019","journal-title":"Front Immunol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1038\/scientificamerican0773-52","article-title":"The immune system","volume":"229","author":"Jerne","year":"1973","journal-title":"Sci Am"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/0090-1229(89)90197-9","article-title":"Revised immune network concepts","volume":"52","author":"K\u00f6hler","year":"1989","journal-title":"Clin Immunol Immunopathol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830050511","article-title":"A network theory of the immune system","volume":"5","author":"Richter","year":"1975","journal-title":"Eur J Immunol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830050912","article-title":"A theory of regulation and self-nonself discrimination in an immune network","volume":"5","author":"Hoffmann","year":"1975","journal-title":"Eur J Immunol"},{"key":"B6","article-title":"Towards a network theory of the immune system","author":"Jerne","year":"1974","journal-title":"Ann Immunol (Paris)"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1126\/science.140.3572.1218","article-title":"Individual antigenic specificity of isolated antibodies","volume":"140","author":"Kunkel","year":"1963","journal-title":"Science"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1084\/jem.132.4.737","article-title":"Common individual antigenic determinants in five of eight BALB-c IgA myeloma proteins that bind phosphoryl choline","volume":"132","author":"Potter","year":"1970","journal-title":"J Exp Med"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.69.9.2701","article-title":"Specific suppression of the antibody response by antibodies to receptors","volume":"69","author":"Cosenza","year":"1972","journal-title":"Proc Natl Acad Sci U.S.A"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1126\/science.176.4038.1027","article-title":"Specific inhibition of plaque formation to phosphorylcholine by antibody against antibody","volume":"176","author":"Cosenza","year":"1972","journal-title":"Science"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1126\/science.186.4164.640","article-title":"Neonatal tolerance induced by antibody against antigen-specific receptor","volume":"186","author":"Strayer","year":"1974","journal-title":"Science"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1126\/science.186.4164.643","article-title":"Clonal depletion in neonatal tolerance. 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