{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T00:23:11Z","timestamp":1790209391478,"version":"4.1.0"},"reference-count":38,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2006,11,1]],"date-time":"2006-11-01T00:00:00Z","timestamp":1162339200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2006,11,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Inaccurate VDJ rearrangements generate a large number of progenitor (pro)-B cells with two nonproductive IgH alleles. Such cells lack essential survival signals mediated by surface IgM heavy chain (\u03bcH chain) expression and are normally eliminated. However, secondary rearrangements of upstream VH gene segments into assembled VDJ exons have been described in mice transgenic for productive \u03bcH chains, a process known as VH replacement. If VH replacement was independent of \u03bcH chain signals, it could also modify nonproductive VDJ exons and thus rescue pro-B cells with unsuccessful rearrangements on both alleles. To test this hypothesis, we homologously replaced the JH cluster of a mouse with a nonproductive VDJ exon. Surprisingly, B cell development in IgHVDJ\u2212\/VDJ\u2212 mice was only slightly impaired and significant numbers of IgM-positive B cells were produced. DNA sequencing confirmed that all VDJ sequences from \u03bcH chain-positive B lymphoid cells were generated by VH replacement in a RAG-dependent manner. Another unique feature of our transgenic mice was the presence of IgH chains with unusually long CDR3-H regions. Such IgH chains were functional and only modestly counter-selected, arguing against a strict length constraint for CDR3-H regions. In conclusion, VH replacement can occur in the absence of a \u03bcH chain signal and provides a potential rescue mechanism for pro-B cells with two nonproductive IgH alleles.<\/jats:p>","DOI":"10.4049\/jimmunol.177.10.7007","type":"journal-article","created":{"date-parts":[[2014,4,18]],"date-time":"2014-04-18T19:39:04Z","timestamp":1397849944000},"page":"7007-7014","source":"Crossref","is-referenced-by-count":18,"title":["VH Replacement Rescues Progenitor B Cells with Two Nonproductive VDJ Alleles"],"prefix":"10.1093","volume":"177","author":[{"given":"Johannes","family":"Lutz","sequence":"first","affiliation":[{"name":"Division of Molecular Immunology, Department of Internal Medicine III, Nikolaus-Fiebiger-Center of Molecular Medicine, Friedrich-Alexander-University Erlangen-Nu\u0308rnberg , Erlangen ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Werner","family":"Mu\u0308ller","sequence":"additional","affiliation":[{"name":"Department of Experimental Immunology, German Research Centre for Biotechnology , Braunschweig ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans-Martin","family":"Ja\u0308ck","sequence":"additional","affiliation":[{"name":"Division of Molecular Immunology, Department of Internal Medicine III, Nikolaus-Fiebiger-Center of Molecular Medicine, Friedrich-Alexander-University Erlangen-Nu\u0308rnberg , Erlangen ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2006,11,15]]},"reference":[{"key":"2026020214064304800_R1","first-page":"541","volume-title":"Annu. 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