Secondary heavy chain rearrangement: a mechanism for generating anti-double-stranded DNA B cells
The chronic graft-versus-host (cGVH) reaction results in a syndrome that closely resembles systemic lupus erythematosus (SLE). It is induced in nonautoimmune mice by the transfer of alloreactive T cells. The availability of anti-DNA transgenes allows us to study the genetic origins of autoantibodies...
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| Veröffentlicht in: | The Journal of experimental medicine 2003-01, Vol.197 (1), p.27-39 |
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| container_title | The Journal of experimental medicine |
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| creator | Sekiguchi, Debora R Eisenberg, Robert A Weigert, Martin |
| description | The chronic graft-versus-host (cGVH) reaction results in a syndrome that closely resembles systemic lupus erythematosus (SLE). It is induced in nonautoimmune mice by the transfer of alloreactive T cells. The availability of anti-DNA transgenes allows us to study the genetic origins of autoantibodies in this model. We induced cGVH in two anti-DNA H chain site-directed transgenic mouse strains. This resulted in clonal expansion and selection of specific mutations in the anti-double-stranded (ds) DNA B cell population. These data, together with a high frequency of anti-dsDNA B cell clones recovered as hybridomas, suggested that anti-dsDNAs are the product of an antigen-driven immune response. Genetic analysis associated this response with the generation of anti-dsDNA B cells through secondary rearrangements that replaced the site-directed transgene (sd-tg) with endogenous VH genes. |
| doi_str_mv | 10.1084/jem.20020737 |
| format | Article |
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It is induced in nonautoimmune mice by the transfer of alloreactive T cells. The availability of anti-DNA transgenes allows us to study the genetic origins of autoantibodies in this model. We induced cGVH in two anti-DNA H chain site-directed transgenic mouse strains. This resulted in clonal expansion and selection of specific mutations in the anti-double-stranded (ds) DNA B cell population. These data, together with a high frequency of anti-dsDNA B cell clones recovered as hybridomas, suggested that anti-dsDNAs are the product of an antigen-driven immune response. Genetic analysis associated this response with the generation of anti-dsDNA B cells through secondary rearrangements that replaced the site-directed transgene (sd-tg) with endogenous VH genes.</description><identifier>ISSN: 0022-1007</identifier><identifier>EISSN: 1540-9538</identifier><identifier>DOI: 10.1084/jem.20020737</identifier><identifier>PMID: 12515811</identifier><language>eng</language><publisher>United States: The Rockefeller University Press</publisher><subject>Amino Acid Sequence ; Animals ; Antibodies, Antinuclear - chemistry ; Antibodies, Antinuclear - genetics ; Antibodies, Antinuclear - immunology ; Antibodies, Monoclonal - immunology ; Antibody Specificity ; B-Lymphocytes - immunology ; Base Sequence ; DNA - immunology ; Enzyme-Linked Immunosorbent Assay ; Gene Rearrangement, B-Lymphocyte - genetics ; Graft vs Host Disease - immunology ; Hybridomas - immunology ; Hybridomas - metabolism ; Immunoglobulin Allotypes - chemistry ; Immunoglobulin Allotypes - genetics ; Immunoglobulin Allotypes - immunology ; Immunoglobulin G - genetics ; Immunoglobulin G - immunology ; Immunoglobulin Heavy Chains - chemistry ; Immunoglobulin Heavy Chains - genetics ; Immunoglobulin Heavy Chains - immunology ; Immunoglobulin Light Chains - chemistry ; Immunoglobulin Light Chains - genetics ; Mice ; Mice, Transgenic ; Molecular Sequence Data ; Mutation - genetics ; Transgenes - genetics</subject><ispartof>The Journal of experimental medicine, 2003-01, Vol.197 (1), p.27-39</ispartof><rights>Copyright © 2003, The Rockefeller University Press</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12515811$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sekiguchi, Debora R</creatorcontrib><creatorcontrib>Eisenberg, Robert A</creatorcontrib><creatorcontrib>Weigert, Martin</creatorcontrib><title>Secondary heavy chain rearrangement: a mechanism for generating anti-double-stranded DNA B cells</title><title>The Journal of experimental medicine</title><addtitle>J Exp Med</addtitle><description>The chronic graft-versus-host (cGVH) reaction results in a syndrome that closely resembles systemic lupus erythematosus (SLE). It is induced in nonautoimmune mice by the transfer of alloreactive T cells. The availability of anti-DNA transgenes allows us to study the genetic origins of autoantibodies in this model. We induced cGVH in two anti-DNA H chain site-directed transgenic mouse strains. This resulted in clonal expansion and selection of specific mutations in the anti-double-stranded (ds) DNA B cell population. These data, together with a high frequency of anti-dsDNA B cell clones recovered as hybridomas, suggested that anti-dsDNAs are the product of an antigen-driven immune response. Genetic analysis associated this response with the generation of anti-dsDNA B cells through secondary rearrangements that replaced the site-directed transgene (sd-tg) with endogenous VH genes.</description><subject>Amino Acid Sequence</subject><subject>Animals</subject><subject>Antibodies, Antinuclear - chemistry</subject><subject>Antibodies, Antinuclear - genetics</subject><subject>Antibodies, Antinuclear - immunology</subject><subject>Antibodies, Monoclonal - immunology</subject><subject>Antibody Specificity</subject><subject>B-Lymphocytes - immunology</subject><subject>Base Sequence</subject><subject>DNA - immunology</subject><subject>Enzyme-Linked Immunosorbent Assay</subject><subject>Gene Rearrangement, B-Lymphocyte - genetics</subject><subject>Graft vs Host Disease - immunology</subject><subject>Hybridomas - immunology</subject><subject>Hybridomas - metabolism</subject><subject>Immunoglobulin Allotypes - chemistry</subject><subject>Immunoglobulin Allotypes - genetics</subject><subject>Immunoglobulin Allotypes - immunology</subject><subject>Immunoglobulin G - genetics</subject><subject>Immunoglobulin G - immunology</subject><subject>Immunoglobulin Heavy Chains - chemistry</subject><subject>Immunoglobulin Heavy Chains - genetics</subject><subject>Immunoglobulin Heavy Chains - immunology</subject><subject>Immunoglobulin Light Chains - chemistry</subject><subject>Immunoglobulin Light Chains - genetics</subject><subject>Mice</subject><subject>Mice, Transgenic</subject><subject>Molecular Sequence Data</subject><subject>Mutation - genetics</subject><subject>Transgenes - genetics</subject><issn>0022-1007</issn><issn>1540-9538</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFUD1PwzAUtBCIlo-NGXliS7EdO3YYkEr5lCoYgDk4yUvqKnGKnVTqv8eIgmBiek939053D6ETSiaUKH6-hHbCCGFExnIHjangJEpFrHbROKAsooTIETrwfkkI5Vwk-2hEmaBCUTpGb89QdLbUboMXoNcbXCy0sdiBdk7bGlqw_QXWuIVAWONbXHUO12DB6d7YGmvbm6jshryByPfhpoQSXz9O8RUuoGn8EdqrdOPheDsP0evtzcvsPpo_3T3MpvNoxdK4j5KKaMGZJCJnkGulVEJTlSsumAy4JpTmSqs8iKqwVyAlk3kZk7JMZULi-BBdfvmuhryFsgi5nW6ylTNtKJd12mR_GWsWWd2tM0bTWBERDM62Bq57H8D3WWv8ZwVtoRt8JlnKhVDsXyFVieIhURCe_o70k-X7-_EHe0eG6w</recordid><startdate>20030106</startdate><enddate>20030106</enddate><creator>Sekiguchi, Debora R</creator><creator>Eisenberg, Robert A</creator><creator>Weigert, Martin</creator><general>The Rockefeller University Press</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7T5</scope><scope>H94</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20030106</creationdate><title>Secondary heavy chain rearrangement: a mechanism for generating anti-double-stranded DNA B cells</title><author>Sekiguchi, Debora R ; Eisenberg, Robert A ; Weigert, Martin</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p293t-6f0a542705b2eba8886198b84527542a011b8a8ba54f011fe7727bd30dd976033</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Amino Acid Sequence</topic><topic>Animals</topic><topic>Antibodies, Antinuclear - chemistry</topic><topic>Antibodies, Antinuclear - genetics</topic><topic>Antibodies, Antinuclear - immunology</topic><topic>Antibodies, Monoclonal - immunology</topic><topic>Antibody Specificity</topic><topic>B-Lymphocytes - immunology</topic><topic>Base Sequence</topic><topic>DNA - immunology</topic><topic>Enzyme-Linked Immunosorbent Assay</topic><topic>Gene Rearrangement, B-Lymphocyte - genetics</topic><topic>Graft vs Host Disease - immunology</topic><topic>Hybridomas - immunology</topic><topic>Hybridomas - metabolism</topic><topic>Immunoglobulin Allotypes - chemistry</topic><topic>Immunoglobulin Allotypes - genetics</topic><topic>Immunoglobulin Allotypes - immunology</topic><topic>Immunoglobulin G - genetics</topic><topic>Immunoglobulin G - immunology</topic><topic>Immunoglobulin Heavy Chains - chemistry</topic><topic>Immunoglobulin Heavy Chains - genetics</topic><topic>Immunoglobulin Heavy Chains - immunology</topic><topic>Immunoglobulin Light Chains - chemistry</topic><topic>Immunoglobulin Light Chains - genetics</topic><topic>Mice</topic><topic>Mice, Transgenic</topic><topic>Molecular Sequence Data</topic><topic>Mutation - genetics</topic><topic>Transgenes - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sekiguchi, Debora R</creatorcontrib><creatorcontrib>Eisenberg, Robert A</creatorcontrib><creatorcontrib>Weigert, Martin</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of experimental medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sekiguchi, Debora R</au><au>Eisenberg, Robert A</au><au>Weigert, Martin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Secondary heavy chain rearrangement: a mechanism for generating anti-double-stranded DNA B cells</atitle><jtitle>The Journal of experimental medicine</jtitle><addtitle>J Exp Med</addtitle><date>2003-01-06</date><risdate>2003</risdate><volume>197</volume><issue>1</issue><spage>27</spage><epage>39</epage><pages>27-39</pages><issn>0022-1007</issn><eissn>1540-9538</eissn><abstract>The chronic graft-versus-host (cGVH) reaction results in a syndrome that closely resembles systemic lupus erythematosus (SLE). 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| identifier | ISSN: 0022-1007 |
| ispartof | The Journal of experimental medicine, 2003-01, Vol.197 (1), p.27-39 |
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| language | eng |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | Amino Acid Sequence Animals Antibodies, Antinuclear - chemistry Antibodies, Antinuclear - genetics Antibodies, Antinuclear - immunology Antibodies, Monoclonal - immunology Antibody Specificity B-Lymphocytes - immunology Base Sequence DNA - immunology Enzyme-Linked Immunosorbent Assay Gene Rearrangement, B-Lymphocyte - genetics Graft vs Host Disease - immunology Hybridomas - immunology Hybridomas - metabolism Immunoglobulin Allotypes - chemistry Immunoglobulin Allotypes - genetics Immunoglobulin Allotypes - immunology Immunoglobulin G - genetics Immunoglobulin G - immunology Immunoglobulin Heavy Chains - chemistry Immunoglobulin Heavy Chains - genetics Immunoglobulin Heavy Chains - immunology Immunoglobulin Light Chains - chemistry Immunoglobulin Light Chains - genetics Mice Mice, Transgenic Molecular Sequence Data Mutation - genetics Transgenes - genetics |
| title | Secondary heavy chain rearrangement: a mechanism for generating anti-double-stranded DNA B cells |
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