Reshaping the murine immunoglobulin heavy chain repertoire with bovine DH genes
Having a limited number of VH segments, cattle rely on uniquely long DH gene segments to generate CDRH3 length variation (3–70 aa) far greater than that in humans or mice. Bovine antibodies with ultralong CDRH3s (>50 aa) possess unusual structures and abilities to bind to special antigens. In thi...
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| Veröffentlicht in: | Immunology 2022-01, Vol.165 (1), p.74-87 |
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| creator | Di, Yu Cai, Shuyi Zheng, Shunan Huang, Jinwei Du, Lijuan Song, Yu Zhang, Ming Wang, Zhao Yu, Guotao Ren, Liming Han, Haitang Zhao, Yaofeng |
| description | Having a limited number of VH segments, cattle rely on uniquely long DH gene segments to generate CDRH3 length variation (3–70 aa) far greater than that in humans or mice. Bovine antibodies with ultralong CDRH3s (>50 aa) 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‐DH. The use of bovine DH genes significantly increased the length variation of CDRH3 and consequently the Ig heavy chain repertoire in B‐DH mice. However, no ultralong CDRH3 was observed in B‐DH mice, suggesting that other factors, in addition to long DH genes, are also involved in the formation of ultralong CDRH3. The B‐DH mice mounted a normal humoral immune response to various antigens, although the B‐cell developmental paradigm was obviously altered compared with wild‐type mice. Additionally, B‐DH mice are not predisposed to the generation of autoantibodies despite the interspecies DH gene replacement. The B‐DH 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‐cell development.
The use of bovine DH genes significantly reshaped the Ig heavy chain repertoire in mice. However, no ultralong CDRH3 was observed, suggesting that other factors, in addition to long DH genes, are also involved in the formation of ultralong CDRH3. |
| doi_str_mv | 10.1111/imm.13407 |
| format | Article |
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The use of bovine DH genes significantly reshaped the Ig heavy chain repertoire in mice. However, no ultralong CDRH3 was observed, suggesting that other factors, in addition to long DH genes, are also involved in the formation of ultralong CDRH3.</description><identifier>ISSN: 0019-2805</identifier><identifier>EISSN: 1365-2567</identifier><identifier>DOI: 10.1111/imm.13407</identifier><identifier>PMID: 34428313</identifier><language>eng</language><publisher>England: Wiley Subscription Services, Inc</publisher><subject>Animals ; Antibodies ; Antibody Formation - genetics ; Antibody Formation - immunology ; Antigens ; Autoantibodies ; B-Lymphocytes - immunology ; B-Lymphocytes - metabolism ; B‐cell development ; Cattle ; Chains ; Complementarity Determining Regions - genetics ; Complementarity Determining Regions - immunology ; DH gene ; Evolutionary genetics ; Gene Targeting ; Genes ; Genetic Loci ; Genetic Vectors - genetics ; Ig repertoire ; Immune response ; Immune response (humoral) ; Immune system ; Immunity, Humoral ; immunoglobulin ; Immunoglobulin Heavy Chains - genetics ; Immunoglobulin Heavy Chains - immunology ; Immunoglobulin Variable Region - genetics ; Immunoglobulins ; Mice ; Mice, Transgenic ; Segments ; ultralong CDRH3 ; V(D)J Recombination</subject><ispartof>Immunology, 2022-01, Vol.165 (1), p.74-87</ispartof><rights>2021 John Wiley & Sons Ltd</rights><rights>2021 John Wiley & Sons Ltd.</rights><rights>Copyright © 2022 John Wiley & Sons Ltd</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3887-9bdf1a08fcad6c52774dc1cf8d64275863ee46cea33adc7da77e44283091e8533</citedby><cites>FETCH-LOGICAL-c3887-9bdf1a08fcad6c52774dc1cf8d64275863ee46cea33adc7da77e44283091e8533</cites><orcidid>0000-0003-4499-8610</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fimm.13407$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fimm.13407$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,1427,27903,27904,45553,45554,46387,46811</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34428313$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Di, Yu</creatorcontrib><creatorcontrib>Cai, Shuyi</creatorcontrib><creatorcontrib>Zheng, Shunan</creatorcontrib><creatorcontrib>Huang, Jinwei</creatorcontrib><creatorcontrib>Du, Lijuan</creatorcontrib><creatorcontrib>Song, Yu</creatorcontrib><creatorcontrib>Zhang, Ming</creatorcontrib><creatorcontrib>Wang, Zhao</creatorcontrib><creatorcontrib>Yu, Guotao</creatorcontrib><creatorcontrib>Ren, Liming</creatorcontrib><creatorcontrib>Han, Haitang</creatorcontrib><creatorcontrib>Zhao, Yaofeng</creatorcontrib><title>Reshaping the murine immunoglobulin heavy chain repertoire with bovine DH genes</title><title>Immunology</title><addtitle>Immunology</addtitle><description>Having a limited number of VH segments, cattle rely on uniquely long DH gene segments to generate CDRH3 length variation (3–70 aa) far greater than that in humans or mice. Bovine antibodies with ultralong CDRH3s (>50 aa) 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‐DH. The use of bovine DH genes significantly increased the length variation of CDRH3 and consequently the Ig heavy chain repertoire in B‐DH mice. However, no ultralong CDRH3 was observed in B‐DH mice, suggesting that other factors, in addition to long DH genes, are also involved in the formation of ultralong CDRH3. The B‐DH mice mounted a normal humoral immune response to various antigens, although the B‐cell developmental paradigm was obviously altered compared with wild‐type mice. Additionally, B‐DH mice are not predisposed to the generation of autoantibodies despite the interspecies DH gene replacement. The B‐DH 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‐cell development.
The use of bovine DH genes significantly reshaped the Ig heavy chain repertoire in mice. However, no ultralong CDRH3 was observed, suggesting that other factors, in addition to long DH genes, are also involved in the formation of ultralong CDRH3.</description><subject>Animals</subject><subject>Antibodies</subject><subject>Antibody Formation - genetics</subject><subject>Antibody Formation - immunology</subject><subject>Antigens</subject><subject>Autoantibodies</subject><subject>B-Lymphocytes - immunology</subject><subject>B-Lymphocytes - metabolism</subject><subject>B‐cell development</subject><subject>Cattle</subject><subject>Chains</subject><subject>Complementarity Determining Regions - genetics</subject><subject>Complementarity Determining Regions - immunology</subject><subject>DH gene</subject><subject>Evolutionary genetics</subject><subject>Gene Targeting</subject><subject>Genes</subject><subject>Genetic Loci</subject><subject>Genetic Vectors - genetics</subject><subject>Ig repertoire</subject><subject>Immune response</subject><subject>Immune response (humoral)</subject><subject>Immune system</subject><subject>Immunity, Humoral</subject><subject>immunoglobulin</subject><subject>Immunoglobulin Heavy Chains - genetics</subject><subject>Immunoglobulin Heavy Chains - immunology</subject><subject>Immunoglobulin Variable Region - genetics</subject><subject>Immunoglobulins</subject><subject>Mice</subject><subject>Mice, Transgenic</subject><subject>Segments</subject><subject>ultralong CDRH3</subject><subject>V(D)J Recombination</subject><issn>0019-2805</issn><issn>1365-2567</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kMtKAzEUQIMotlYX_oAMuNHFtMkkM8kspT5aaCmIrkOaudNJmUdNOi39e9OHLgSzSS6cHC4HoVuC-8SfgamqPqEM8zPUJTSJwyhO-DnqYkzSMBI47qAr55Z-pDiOL1GHMhYJSmgXzd7BFWpl6kWwLiCoWmtqCLywrZtF2czb0tRBAWqzC3Sh_NvCCuy6MRaCrVkXwbzZ7H88j4IF1OCu0UWuSgc3p7uHPl9fPoajcDJ7Gw-fJqGmQvAwnWc5UVjkWmWJjiPOWaaJzkWWsIjHIqEALNGgKFWZ5pniHA4745SAiCntoYejd2WbrxbcWlbGaShLVUPTOukLMJYyIohH7_-gy6a1td9ORglOmRA44p56PFLaNs5ZyOXKmkrZnSRY7itLH0UeKnv27mRs5xVkv-RPVg8MjsDWlLD73yTH0-lR-Q3EqIXf</recordid><startdate>202201</startdate><enddate>202201</enddate><creator>Di, Yu</creator><creator>Cai, Shuyi</creator><creator>Zheng, Shunan</creator><creator>Huang, Jinwei</creator><creator>Du, Lijuan</creator><creator>Song, Yu</creator><creator>Zhang, Ming</creator><creator>Wang, Zhao</creator><creator>Yu, Guotao</creator><creator>Ren, Liming</creator><creator>Han, Haitang</creator><creator>Zhao, Yaofeng</creator><general>Wiley Subscription Services, Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QL</scope><scope>7QR</scope><scope>7T5</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-4499-8610</orcidid></search><sort><creationdate>202201</creationdate><title>Reshaping the murine immunoglobulin heavy chain repertoire with bovine DH genes</title><author>Di, Yu ; Cai, Shuyi ; Zheng, Shunan ; Huang, Jinwei ; Du, Lijuan ; Song, Yu ; Zhang, Ming ; Wang, Zhao ; Yu, Guotao ; Ren, Liming ; Han, Haitang ; Zhao, Yaofeng</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3887-9bdf1a08fcad6c52774dc1cf8d64275863ee46cea33adc7da77e44283091e8533</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Animals</topic><topic>Antibodies</topic><topic>Antibody Formation - genetics</topic><topic>Antibody Formation - immunology</topic><topic>Antigens</topic><topic>Autoantibodies</topic><topic>B-Lymphocytes - immunology</topic><topic>B-Lymphocytes - metabolism</topic><topic>B‐cell development</topic><topic>Cattle</topic><topic>Chains</topic><topic>Complementarity Determining Regions - genetics</topic><topic>Complementarity Determining Regions - immunology</topic><topic>DH gene</topic><topic>Evolutionary genetics</topic><topic>Gene Targeting</topic><topic>Genes</topic><topic>Genetic Loci</topic><topic>Genetic Vectors - genetics</topic><topic>Ig repertoire</topic><topic>Immune response</topic><topic>Immune response (humoral)</topic><topic>Immune system</topic><topic>Immunity, Humoral</topic><topic>immunoglobulin</topic><topic>Immunoglobulin Heavy Chains - genetics</topic><topic>Immunoglobulin Heavy Chains - immunology</topic><topic>Immunoglobulin Variable Region - genetics</topic><topic>Immunoglobulins</topic><topic>Mice</topic><topic>Mice, Transgenic</topic><topic>Segments</topic><topic>ultralong CDRH3</topic><topic>V(D)J Recombination</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Di, Yu</creatorcontrib><creatorcontrib>Cai, Shuyi</creatorcontrib><creatorcontrib>Zheng, Shunan</creatorcontrib><creatorcontrib>Huang, Jinwei</creatorcontrib><creatorcontrib>Du, Lijuan</creatorcontrib><creatorcontrib>Song, Yu</creatorcontrib><creatorcontrib>Zhang, Ming</creatorcontrib><creatorcontrib>Wang, Zhao</creatorcontrib><creatorcontrib>Yu, Guotao</creatorcontrib><creatorcontrib>Ren, Liming</creatorcontrib><creatorcontrib>Han, Haitang</creatorcontrib><creatorcontrib>Zhao, Yaofeng</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Chemoreception Abstracts</collection><collection>Immunology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Immunology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Di, Yu</au><au>Cai, Shuyi</au><au>Zheng, Shunan</au><au>Huang, Jinwei</au><au>Du, Lijuan</au><au>Song, Yu</au><au>Zhang, Ming</au><au>Wang, Zhao</au><au>Yu, Guotao</au><au>Ren, Liming</au><au>Han, Haitang</au><au>Zhao, Yaofeng</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Reshaping the murine immunoglobulin heavy chain repertoire with bovine DH genes</atitle><jtitle>Immunology</jtitle><addtitle>Immunology</addtitle><date>2022-01</date><risdate>2022</risdate><volume>165</volume><issue>1</issue><spage>74</spage><epage>87</epage><pages>74-87</pages><issn>0019-2805</issn><eissn>1365-2567</eissn><abstract>Having a limited number of VH segments, cattle rely on uniquely long DH gene segments to generate CDRH3 length variation (3–70 aa) far greater than that in humans or mice. Bovine antibodies with ultralong CDRH3s (>50 aa) 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‐DH. The use of bovine DH genes significantly increased the length variation of CDRH3 and consequently the Ig heavy chain repertoire in B‐DH mice. However, no ultralong CDRH3 was observed in B‐DH mice, suggesting that other factors, in addition to long DH genes, are also involved in the formation of ultralong CDRH3. The B‐DH mice mounted a normal humoral immune response to various antigens, although the B‐cell developmental paradigm was obviously altered compared with wild‐type mice. Additionally, B‐DH mice are not predisposed to the generation of autoantibodies despite the interspecies DH gene replacement. The B‐DH 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‐cell development.
The use of bovine DH genes significantly reshaped the Ig heavy chain repertoire in mice. However, no ultralong CDRH3 was observed, suggesting that other factors, in addition to long DH genes, are also involved in the formation of ultralong CDRH3.</abstract><cop>England</cop><pub>Wiley Subscription Services, Inc</pub><pmid>34428313</pmid><doi>10.1111/imm.13407</doi><tpages>14</tpages><orcidid>https://orcid.org/0000-0003-4499-8610</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Antibodies Antibody Formation - genetics Antibody Formation - immunology Antigens Autoantibodies B-Lymphocytes - immunology B-Lymphocytes - metabolism B‐cell development Cattle Chains Complementarity Determining Regions - genetics Complementarity Determining Regions - immunology DH gene Evolutionary genetics Gene Targeting Genes Genetic Loci Genetic Vectors - genetics Ig repertoire Immune response Immune response (humoral) Immune system Immunity, Humoral immunoglobulin Immunoglobulin Heavy Chains - genetics Immunoglobulin Heavy Chains - immunology Immunoglobulin Variable Region - genetics Immunoglobulins Mice Mice, Transgenic Segments ultralong CDRH3 V(D)J Recombination |
| title | Reshaping the murine immunoglobulin heavy chain repertoire with bovine DH genes |
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