{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T00:48:41Z","timestamp":1776041321532,"version":"3.50.1"},"reference-count":42,"publisher":"Rockefeller University Press","issue":"11","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2004,6,7]]},"abstract":"<jats:p>Early B cell development is characterized by stepwise, ordered rearrangement of the immunoglobulin (Ig) heavy (HC) and light (LC) chain genes. Only one of the two alleles of these genes is used to produce a receptor, a phenomenon referred to as allelic exclusion. It has been suggested that pre\u2013B cell receptor (pre-BCR) signals are responsible for down-regulation of the VDJH-recombinase machinery (Rag1, Rag2, and terminal deoxynucleotidyl transferase [TdT]), thereby preventing further rearrangement on the second HC allele. Using a mouse model, we show that expression of an inducible \u03bcHC transgene in Rag2\u2212\/\u2212 pro\u2013B cells induces down-regulation of the following: (a) TdT protein, (b) a transgenic green fluorescent protein reporter reflecting endogenous Rag2 expression, and (c) Rag1 primary transcripts. Similar effects were also observed in the absence of surrogate LC (SLC) components, but not in the absence of the signaling subunit Ig-\u03b1. Furthermore, in wild-type mice and in mice lacking either \u03bb5, VpreB1\/2, or the entire SLC, the TdT protein is down-regulated in \u03bcHC+LC\u2212 pre\u2013B cells. Surprisingly, \u03bcHC without LC is expressed on the surface of pro\u2013\/pre\u2013B cells from \u03bb5\u2212\/\u2212, VpreB1\u2212\/\u2212VpreB2\u2212\/\u2212, and SLC\u2212\/\u2212 mice. Thus, SLC or LC is not required for \u03bcHC cell surface expression and signaling in these cells. Therefore, these findings offer an explanation for the occurrence of HC allelic exclusion in mice lacking SLC components.<\/jats:p>","DOI":"10.1084\/jem.20031523","type":"journal-article","created":{"date-parts":[[2004,6,7]],"date-time":"2004-06-07T22:53:10Z","timestamp":1086648790000},"page":"1523-1532","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":48,"title":["Surface \u03bc Heavy Chain Signals Down-Regulation of the V(D)J-Recombinase Machinery in the Absence of Surrogate Light Chain Components"],"prefix":"10.1084","volume":"199","author":[{"given":"Gunther R.","family":"Galler","sequence":"first","affiliation":[{"name":"1Hematopoiesis Unit, Nikolaus-Fiebiger-Center, Friedrich-Alexander University, 91054 Erlangen, Germany"}]},{"given":"Cornelia","family":"Mundt","sequence":"additional","affiliation":[{"name":"2Developmental Immunology, The Babraham Institute, Babraham, CB2 4AT Cambridge, England, UK"}]},{"given":"Mathew","family":"Parker","sequence":"additional","affiliation":[{"name":"2Developmental Immunology, The Babraham Institute, Babraham, CB2 4AT Cambridge, England, UK"}]},{"given":"Roberta","family":"Pelanda","sequence":"additional","affiliation":[{"name":"3Department of Immunology, National Jewish Medical and Research Center, University of Colorado Health Sciences Center, Denver, CO 80206"}]},{"given":"Inga-Lill","family":"Ma\u030artensson","sequence":"additional","affiliation":[{"name":"2Developmental Immunology, The Babraham Institute, Babraham, CB2 4AT Cambridge, England, UK"}]},{"given":"Thomas H.","family":"Winkler","sequence":"additional","affiliation":[{"name":"1Hematopoiesis Unit, Nikolaus-Fiebiger-Center, Friedrich-Alexander University, 91054 Erlangen, Germany"}]}],"member":"291","published-online":{"date-parts":[[2004,6,1]]},"reference":[{"key":"2023072512150552300_BIB1","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.1002\/j.1460-2075.1984.tb01955.x","volume":"3","year":"1984","journal-title":"EMBO J."},{"key":"2023072512150552300_BIB2","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1146\/annurev.iy.12.040194.001233","volume":"12","year":"1994","journal-title":"Annu. 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