{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T16:29:01Z","timestamp":1781108941878,"version":"3.54.1"},"reference-count":0,"publisher":"National Academy of Sciences","issue":"25","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1994,12,6]]},"abstract":"<jats:p>To study the role of B-cell antigen CD40 in immune responses, mouse embryonic stem (ES) cells in which both copies of the gene encoding CD40 had been disrupted by homologous recombination were injected in RAG-2 (recombination-activating gene-2)-deficient blastocysts to generate chimeras in which all mature lymphocytes are derived from the CD40-deficient ES cells. T- and B-cell number and phenotype were normal in the CD40-\/- chimeras. However, B cells failed to proliferate and undergo isotype switching in vitro in response to soluble CD40 ligand (sCD40L) with interleukin 4 (IL-4) but responded normally to lipopolysaccharide (LPS) with IL-4. CD40-\/- chimeras completely failed to mount an antigen-specific antibody response or to develop germinal centers following immunization with the T cell-dependent (TD) antigen keyhole limpet hemocyanin. In contrast, CD40-\/- mutant mice responded normally to the T cell-independent (TI) antigens, 2,4,6-trinitrophenyl (TNP)-LPS and TNP-Ficoll. The most noticeable alteration in the serum immunoglobulin levels of young (6-8 weeks old) CD40-\/- animals was absence of IgE and severe decrease of IgG1 and IgG2a. These results confirm the essential role of CD40- CD40L interactions in the antibody response to TD antigens and in isotype switching.<\/jats:p>","DOI":"10.1073\/pnas.91.25.12135","type":"journal-article","created":{"date-parts":[[2006,5,31]],"date-time":"2006-05-31T09:01:32Z","timestamp":1149066092000},"page":"12135-12139","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":168,"title":["CD40-deficient mice generated by recombination-activating gene-2-deficient blastocyst complementation."],"prefix":"10.1073","volume":"91","author":[{"given":"E","family":"Castigli","sequence":"first","affiliation":[{"name":"Division of Immunology, Children's Hospital, Boston, MA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F W","family":"Alt","sequence":"additional","affiliation":[{"name":"Division of Immunology, Children's Hospital, Boston, MA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L","family":"Davidson","sequence":"additional","affiliation":[{"name":"Division of Immunology, Children's Hospital, Boston, MA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Bottaro","sequence":"additional","affiliation":[{"name":"Division of Immunology, Children's Hospital, Boston, MA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E","family":"Mizoguchi","sequence":"additional","affiliation":[{"name":"Division of Immunology, Children's Hospital, Boston, MA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A K","family":"Bhan","sequence":"additional","affiliation":[{"name":"Division of Immunology, Children's Hospital, Boston, MA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R S","family":"Geha","sequence":"additional","affiliation":[{"name":"Division of Immunology, Children's Hospital, Boston, MA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[1994,12,6]]},"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.91.25.12135","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T14:11:45Z","timestamp":1649859105000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.91.25.12135"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1994,12,6]]},"references-count":0,"journal-issue":{"issue":"25","published-print":{"date-parts":[[1994,12,6]]}},"alternative-id":["10.1073\/pnas.91.25.12135"],"URL":"https:\/\/doi.org\/10.1073\/pnas.91.25.12135","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[1994,12,6]]},"assertion":[{"value":"1994-12-06","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}