{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T04:13:59Z","timestamp":1790396039088,"version":"4.1.0"},"reference-count":3,"publisher":"S. Karger AG","issue":"2-4","license":[{"start":{"date-parts":[[1999,1,1]],"date-time":"1999-01-01T00:00:00Z","timestamp":915148800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[1999,1,1]],"date-time":"1999-01-01T00:00:00Z","timestamp":915148800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int Arch Allergy Immunol"],"published-print":{"date-parts":[[1999]]},"abstract":"<jats:p>&lt;b&gt;Background: &lt;\/b&gt;Allergic reactions occur rarely in patients with chronic helminth infections, although Fc\u03b5RI\u2013bearing cells are sensitized with anti\u2013parasite IgE and are exposed to antigen. The inhibition of allergic reactivity is due to \u2018blocking antibodies\u2019, predominantly IgG4. IgG4 antibodies represent 50\u201395% of anti\u2013filarial IgG, and have blocking activity because they compete with cell\u2013bound IgE for allergen binding. Blocking IgG4 antibodies have also been detected in patients treated with immunotherapy. However, the molecular mechanisms of IgG4 regulation have remained unexplored. We address this issue starting with the IL\u20134\u2013dependent induction of \u03b34 germline transcription, an essential step in the commitment to isotype switching. &lt;b&gt;Results: &lt;\/b&gt;\u03b34 germline transcripts were cloned and shown to contain I\u03b34 spliced to the 5\u2032 portion of C\u03b34 using the splice donor site shared by \u03b31 and \u03b33 germline transcripts. Sequence analysis located the human I\u03b34 exon \u22480.6 kb upstream of the S\u03b34 region. Four major transcription start sites located 547\u2013583 bp upstream of the I\u03b34 splice donor site were identified by primer extension analysis. A &lt;i&gt;Hind&lt;\/i&gt;III\/&lt;i&gt;Nae&lt;\/i&gt;I construct (\u2013413\/+466) had the highest activity in reporter assays. Transcription was induced 4.6\u2013fold by IL\u20134, 2.1\u2013fold by CD40 engagement, and 14.5\u2013fold by a combination of the two signals. Thus CD40 crosslinking enhanced IL\u20134\u2013dependent transcription by 3.1\u2013fold, showing that the two stimuli act synergistically. &lt;b&gt;Conclusion: &lt;\/b&gt;As we understand more about IgG4 regulation, our hope is to apply to allergy the lesson we learnt from helminth infections.<\/jats:p>","DOI":"10.1159\/000024099","type":"journal-article","created":{"date-parts":[[2003,4,15]],"date-time":"2003-04-15T10:10:37Z","timestamp":1050401437000},"page":"279-281","source":"Crossref","is-referenced-by-count":29,"title":["Analysis of \u03b34 Germline Transcription in Human B Cells"],"prefix":"10.1159","volume":"118","author":[{"given":"Alessandra","family":"Agresti","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donata","family":"Vercelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"127","published-online":{"date-parts":[[1999,4,23]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-1759(86)90217-6"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1159\/000023984"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1084\/jem.172.2.463"}],"container-title":["International Archives of Allergy and Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/24099","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/24099","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T04:54:54Z","timestamp":1745470494000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000024099"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1999]]},"references-count":3,"journal-issue":{"issue":"2-4","published-online":{"date-parts":[[1999,4,1]]}},"URL":"https:\/\/doi.org\/10.1159\/000024099","archive":["Portico"],"relation":{},"ISSN":["1018-2438","1423-0097"],"issn-type":[{"value":"1018-2438","type":"print"},{"value":"1423-0097","type":"electronic"}],"subject":[],"published":{"date-parts":[[1999]]}}}