{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T13:02:55Z","timestamp":1791205375557,"version":"4.1.0"},"reference-count":0,"publisher":"National Academy of Sciences","issue":"6","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1982,3]]},"abstract":"<jats:p>The clonal anergy theory of induction of immunological tolerance states that differentiating B lymphocytes that encounter multivalent antigen at the pre-B to B cell transition stage can receive and store a negative signal, which renders them anergic to later triggering stimuli. The theory was tested by using an anti-mu chain monoclonal antibody, E4, as a model tolerogen. The fluorescence-activated cell sorter was used to select B cell-free cell populations from adult murine bone marrow or newborn spleen, and later, to analyze B cell neogenesis in vitro. The presence of E4 at greater than or equal to 1 microgram\/ml was required to impede the development of normal numbers of B cells with full receptor status. The subsequent capacity of these B cells to respond in vitro to mitogens was assessed in a filter-cell free microculture system that allows single B cells to proliferate and differentiate. Concentrations of E4 far below those required to affect B cell neogenesis had profound inhibitory effects on the subsequent functional capacity of the B cells. In fact, 10(-3) micrograms\/ml of E4 markedly impaired both proliferation and antibody formation, and 10(-1) micrograms\/ml, which had no effect on Ig receptor development, abrogated functional capacity. Thus B cells formed in the presence of E4 at 10(-1) micrograms\/ml, though possessing the receptor status typical of B cells, were functionally entirely anergic. Exposure to E4 appeared to accelerate the spontaneous death rate of newly formed B cells in vitro. Whether the anergic cell would also have a shortened life span in vivo is not known.<\/jats:p>","DOI":"10.1073\/pnas.79.6.2013","type":"journal-article","created":{"date-parts":[[2006,5,31]],"date-time":"2006-05-31T05:03:20Z","timestamp":1149051800000},"page":"2013-2017","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":79,"title":["Clonal anergy: the universally anergic B lymphocyte."],"prefix":"10.1073","volume":"79","author":[{"given":"B L","family":"Pike","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A W","family":"Boyd","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G J","family":"Nossal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[1982,3]]},"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.79.6.2013","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T11:59:03Z","timestamp":1649851143000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.79.6.2013"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1982,3]]},"references-count":0,"journal-issue":{"issue":"6","published-print":{"date-parts":[[1982,3]]}},"alternative-id":["10.1073\/pnas.79.6.2013"],"URL":"https:\/\/doi.org\/10.1073\/pnas.79.6.2013","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[1982,3]]},"assertion":[{"value":"1982-03-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}