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Bovine antibodies with ultralong CDRH3s (&gt;50\u00a0aa) possess unusual structures and abilities to bind to special antigens. In this study, we replaced most murine endogenous DH segments with bovine DH genes, generating a mouse line termed B\u2010DH. The use of bovine DH genes significantly increased the length variation of CDRH3 and consequently the Ig heavy chain repertoire in B\u2010DH mice. However, no ultralong CDRH3 was observed in B\u2010DH mice, suggesting that other factors, in addition to long DH genes, are also involved in the formation of ultralong CDRH3. The B\u2010DH mice mounted a normal humoral immune response to various antigens, although the B\u2010cell developmental paradigm was obviously altered compared with wild\u2010type mice. Additionally, B\u2010DH mice are not predisposed to the generation of autoantibodies despite the interspecies DH gene replacement. The B\u2010DH mice reported in this study provide a unique model to answer basic questions regarding the synergistic evolution of DH and VH genes, VDJ recombination and BCR selection in B\u2010cell development.<\/jats:p>","DOI":"10.1111\/imm.13407","type":"journal-article","created":{"date-parts":[[2021,8,24]],"date-time":"2021-08-24T16:44:31Z","timestamp":1629823471000},"page":"74-87","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Reshaping the murine immunoglobulin heavy chain repertoire with bovine DH genes"],"prefix":"10.1111","volume":"165","author":[{"given":"Yu","family":"Di","sequence":"first","affiliation":[{"name":"State Key Laboratory of Agrobiotechnology College of Biological Sciences National Engineering Laboratory for Animal Breeding China Agricultural University  Beijing 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