{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T04:18:19Z","timestamp":1784693899319,"version":"3.55.0"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,8,29]],"date-time":"2025-08-29T00:00:00Z","timestamp":1756425600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100017953","name":"Department of Human Resources and Social Security of Guangxi Zhuang Autonomous Region","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100017953","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>As an important livestock species, sheep exhibit remarkable environmental adaptability. Immunoglobulins, expressed by B cells, are among the most crucial effector molecules in adaptive immunity. However, systematic research on the structure and expression diversity of the sheep immunoglobulins gene loci remains limited. This study annotated the sheep IgH, Ig\u03ba, and Ig\u03bb loci based on the sheep genome assembly (ARS-UI_Ramb_v3.0). The sheep IgH is located on chromosome 18 and comprises 22 VH, 4 DH, and 6 JH. The Ig\u03ba is on chromosome 3, containing 18 V\u03ba and 4 J\u03ba. The Ig\u03bb is situated on chromosome 17 and consists of 128 V\u03bb and 3 J\u03bb. Rearranged IgH, Ig\u03ba, and Ig\u03bb sequences were obtained from sheep spleen using 5\u2019 RACE PCR. Following PE300 high-throughput sequencing, we analyzed the diversity of V, D, J expression diversity, V(D)J recombination, junctional diversity, and somatic hypermutation in the rearranged sequences. For IgH rearrangement, 4 VH, 4 DH, and 2 JH gene segments were utilized, generating 26 distinct rearrangement types. Ig\u03ba rearrangement employed 5 V\u03ba and 3 J\u03ba gene segments, resulting in 13 rearrangement types. Ig\u03bb rearrangement involved 26 V\u03bb and 2 J\u03bb gene segments, producing 28 rearrangement types. Average length of sheep CDR3H is 44 bp (maximum 66 bp), CDR3\u03ba averages 27 bp (maximum 48 bp), and CDR3\u03bb averages 30 bp (maximum 47 bp). N-nucleotide additions contributed more significantly to CDR3 diversity than P-nucleotides in both Ig\u03ba and Ig\u03bb rearrangements. Simultaneously, 3\u2019 V-deletion and 5\u2019 J-deletion further enriched CDR3 diversity. SHM, especially the hotspot mutation motifs, enriches the diversity caused by the V gene segments. Thus, sheep enrich immunoglobulin diversity through both junctional diversity-driven CDR3 diversification and high-intensity SHM. This study expands our understanding of the sheep immunoglobulin gene loci and their expression diversity, providing theoretical foundation for research on immunoglobulin gene evolution within the Bovidae family.<\/jats:p>","DOI":"10.3389\/fimmu.2025.1643380","type":"journal-article","created":{"date-parts":[[2025,8,29]],"date-time":"2025-08-29T04:11:48Z","timestamp":1756440708000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Annotation of gene loci and analysis of expression diversity in sheep immunoglobulin"],"prefix":"10.3389","volume":"16","author":[{"given":"Mingli","family":"Wu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuwen","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqin","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingxuan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haidong","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuelang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,8,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3873","article-title":"Adaptive Immune Receptor Repertoire Community recommendations for sharing immune-repertoire sequencing data","volume":"18","author":"Rubelt","year":"2017","journal-title":"Nat Immunol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1186\/s13073-015-0169-8","article-title":"A bioinformatic framework for immune repertoire diversity profiling enables detection of immunological status","volume":"7","author":"Greiff","year":"2015","journal-title":"Genome Med"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-021-01169-5","article-title":"Diversity in immunogenomics: the value and the challenge","volume":"18","author":"Peng","year":"2021","journal-title":"Nat Methods"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/ni0703-624","article-title":"Gene segment selection in V(D)J recombination: accessibility and beyond","volume":"4","author":"Krangel","year":"2003","journal-title":"Nat Immunol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2009.09.046","article-title":"Structure and function of immunoglobulins","volume":"125","author":"Schroeder","year":"2010","journal-title":"J Allergy Clin Immunol"},{"key":"B6","volume-title":"Janeway's immunobiology","author":"Murphy","year":"2012"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/27.1.209","article-title":"IMGT, the international ImMunoGeneTics database","volume":"27","author":"Lefranc","year":"1999","journal-title":"Nucleic Acids Res"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(14)60720-0","article-title":"IgG4-related disease","volume":"385","author":"Kamisawa","year":"2015","journal-title":"Lancet (London England)"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1038\/nri889","article-title":"Comparative analyses of immunoglobulin genes: surprises and portents","volume":"2","author":"Flajnik","year":"2002","journal-title":"Nat Rev Immunol"},{"key":"B10","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1038\/nrg2703","article-title":"Origin and evolution of the adaptive immune system: genetic events and selective pressures","volume":"11","author":"Flajnik","year":"2010","journal-title":"Nat Rev Immunol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.2782","article-title":"The promise and challenge of high-throughput sequencing of the antibody repertoire","volume":"32","author":"Georgiou","year":"2014","journal-title":"Nat Biotechnol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1038\/nri3804","article-title":"Dynamics of B cells in germinal centres","volume":"15","author":"De Silva","year":"2015","journal-title":"Nat Rev Immunol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1111\/imm.13176","article-title":"V(D)J recombination, somatic hypermutation and class switch recombination of immunoglobulins: mechanism and regulation","volume":"160","author":"Chi","year":"2020","journal-title":"Immunology"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2022.11.013","article-title":"The transcription factor E2A can bind to and cleave single-stranded immunoglobulin heavy chain locus DNA","volume":"153","author":"Grundstr\u00f6m","year":"2023","journal-title":". 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