Genetic Basis for the Cross-Reactive Idiotypes on the Light Chains of Human IgM Anti-IgG Autoantibodies
The role of immunoglobulin structural genes in the generation of autoantibodies in humans has not been elucidated. Human monoclonal IgM anti-IgG autoantibodies (rheumatoid factors, RFs) from unrelated people often share idiotypic antigens. Antibodies against synthetic peptides have localized two of...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 1986-11, Vol.83 (21), p.8318-8322 |
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| container_title | Proceedings of the National Academy of Sciences - PNAS |
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| creator | Chen, Pojen P. Albrandt, Keith Orida, Norman K. Radoux, Victor Chen, Emily Y. Schrantz, Robert Liu, Fu-Tong Carson, Dennis A. |
| description | The role of immunoglobulin structural genes in the generation of autoantibodies in humans has not been elucidated. Human monoclonal IgM anti-IgG autoantibodies (rheumatoid factors, RFs) from unrelated people often share idiotypic antigens. Antibodies against synthetic peptides have localized two of the shared idiotypic determinants to the second and third complementarity-determining regions of the κ light chain. The reported sequences of several human RF light chains are remarkably homologous in these regions. Animal studies have shown that some shared idiotypic antigens represent serological markers for immunoglobulin variable (V)-region genes. Therefore, we hypothesized that human RF light chains derived from a single germ-line gene, designated Vκ(RF) (RF), or from a small family of very closely related genes. In the present experiments, we have isolated and sequenced two human Vκgerm-line genes that encode κ light chains, which are identical or closely related to the light chains of human RF. The data indicate that the shared idiotypic antigens on RF are phenotypic markers for a κ V-region gene that is highly conserved in the human population. The results also imply that the light chains of IgM anti-IgG autoantibodies can be encoded by germ-line genes without any somatic mutation. |
| doi_str_mv | 10.1073/pnas.83.21.8318 |
| format | Article |
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Human monoclonal IgM anti-IgG autoantibodies (rheumatoid factors, RFs) from unrelated people often share idiotypic antigens. Antibodies against synthetic peptides have localized two of the shared idiotypic determinants to the second and third complementarity-determining regions of the κ light chain. The reported sequences of several human RF light chains are remarkably homologous in these regions. Animal studies have shown that some shared idiotypic antigens represent serological markers for immunoglobulin variable (V)-region genes. Therefore, we hypothesized that human RF light chains derived from a single germ-line gene, designated Vκ(RF) (RF), or from a small family of very closely related genes. In the present experiments, we have isolated and sequenced two human Vκgerm-line genes that encode κ light chains, which are identical or closely related to the light chains of human RF. The data indicate that the shared idiotypic antigens on RF are phenotypic markers for a κ V-region gene that is highly conserved in the human population. The results also imply that the light chains of IgM anti-IgG autoantibodies can be encoded by germ-line genes without any somatic mutation.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.83.21.8318</identifier><identifier>PMID: 3095834</identifier><identifier>CODEN: PNASA6</identifier><language>eng</language><publisher>Washington, DC: National Academy of Sciences of the United States of America</publisher><subject>Amino Acid Sequence ; Amino acids ; Antibodies ; Antigens ; Autoantibodies ; Base Sequence ; Biological and medical sciences ; Complementary DNA ; Cross Reactions ; DNA - isolation & purification ; Fundamental and applied biological sciences. Psychology ; Fundamental immunology ; Genes ; Genetics of the immune response ; Humans ; Immunobiology ; Immunoglobulin G - immunology ; Immunoglobulin Idiotypes - genetics ; Immunoglobulin kappa-Chains - genetics ; Immunoglobulin M - immunology ; Immunoglobulin Variable Region - genetics ; Immunoglobulins ; Libraries ; Nucleotides ; Rheumatoid Factor - genetics ; Somatic mutation</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 1986-11, Vol.83 (21), p.8318-8322</ispartof><rights>1987 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c490t-192a962436d0fb731b15b2b6ffbc9bd8f9b74e9a7716c81ad84f0bb4feed8c2b3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/83/21.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/28577$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/28577$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,727,780,784,803,885,27923,27924,53790,53792,58016,58249</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=7973413$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/3095834$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chen, Pojen P.</creatorcontrib><creatorcontrib>Albrandt, Keith</creatorcontrib><creatorcontrib>Orida, Norman K.</creatorcontrib><creatorcontrib>Radoux, Victor</creatorcontrib><creatorcontrib>Chen, Emily Y.</creatorcontrib><creatorcontrib>Schrantz, Robert</creatorcontrib><creatorcontrib>Liu, Fu-Tong</creatorcontrib><creatorcontrib>Carson, Dennis A.</creatorcontrib><title>Genetic Basis for the Cross-Reactive Idiotypes on the Light Chains of Human IgM Anti-IgG Autoantibodies</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>The role of immunoglobulin structural genes in the generation of autoantibodies in humans has not been elucidated. Human monoclonal IgM anti-IgG autoantibodies (rheumatoid factors, RFs) from unrelated people often share idiotypic antigens. Antibodies against synthetic peptides have localized two of the shared idiotypic determinants to the second and third complementarity-determining regions of the κ light chain. The reported sequences of several human RF light chains are remarkably homologous in these regions. Animal studies have shown that some shared idiotypic antigens represent serological markers for immunoglobulin variable (V)-region genes. Therefore, we hypothesized that human RF light chains derived from a single germ-line gene, designated Vκ(RF) (RF), or from a small family of very closely related genes. In the present experiments, we have isolated and sequenced two human Vκgerm-line genes that encode κ light chains, which are identical or closely related to the light chains of human RF. The data indicate that the shared idiotypic antigens on RF are phenotypic markers for a κ V-region gene that is highly conserved in the human population. The results also imply that the light chains of IgM anti-IgG autoantibodies can be encoded by germ-line genes without any somatic mutation.</description><subject>Amino Acid Sequence</subject><subject>Amino acids</subject><subject>Antibodies</subject><subject>Antigens</subject><subject>Autoantibodies</subject><subject>Base Sequence</subject><subject>Biological and medical sciences</subject><subject>Complementary DNA</subject><subject>Cross Reactions</subject><subject>DNA - isolation & purification</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Fundamental immunology</subject><subject>Genes</subject><subject>Genetics of the immune response</subject><subject>Humans</subject><subject>Immunobiology</subject><subject>Immunoglobulin G - immunology</subject><subject>Immunoglobulin Idiotypes - genetics</subject><subject>Immunoglobulin kappa-Chains - genetics</subject><subject>Immunoglobulin M - immunology</subject><subject>Immunoglobulin Variable Region - genetics</subject><subject>Immunoglobulins</subject><subject>Libraries</subject><subject>Nucleotides</subject><subject>Rheumatoid Factor - genetics</subject><subject>Somatic mutation</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1986</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kc2LEzEYxoMoa109C4KSg6yn6eZjOkkOHmpxu4WKIHoOSSZps0yTOsks7n9vxo7FvXjJ1_N73vclDwCvMZpjxOj1Mag053ROcFkxfwJmGAlcNbVAT8EMIcIqXpP6OXiR0h1CSCw4ugAXdDzQegZ2axts9gZ-Uskn6GIP897CVR9Tqr5ZZbK_t3DT-pgfjjbBGP7oW7_bZ7jaKx_Km4O3w0EFuNl9gcuQfbXZreFyyFGVi46tt-kleOZUl-yrab8EP24-f1_dVtuv681qua1MmThXWBAlGlLTpkVOM4o1XmiiG-e0EbrlTmhWW6EYw43hWLW8dkjr2lnbckM0vQQfT3WPgz7Y1tiQe9XJY-8Pqn-QUXn5WAl-L3fxXlLeCCyK_2ry9_HnYFOWB5-M7ToVbBySLI1rxBekgNcn0Ixf1Vt37oGRHKORYzSSU0mwHKMpjrf_jnbmpyyK_n7SVTKqc70KxqczxgSjNaYFezdhY_2_6qM-H_4LSDd0Xba_ciHfnMi7lGN_RglfMEZ_A_9Kucs</recordid><startdate>19861101</startdate><enddate>19861101</enddate><creator>Chen, Pojen P.</creator><creator>Albrandt, Keith</creator><creator>Orida, Norman K.</creator><creator>Radoux, Victor</creator><creator>Chen, Emily Y.</creator><creator>Schrantz, Robert</creator><creator>Liu, Fu-Tong</creator><creator>Carson, Dennis A.</creator><general>National Academy of Sciences of the United States of America</general><general>National Acad Sciences</general><scope>IQODW</scope><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>7X8</scope><scope>5PM</scope></search><sort><creationdate>19861101</creationdate><title>Genetic Basis for the Cross-Reactive Idiotypes on the Light Chains of Human IgM Anti-IgG Autoantibodies</title><author>Chen, Pojen P. ; Albrandt, Keith ; Orida, Norman K. ; Radoux, Victor ; Chen, Emily Y. ; Schrantz, Robert ; Liu, Fu-Tong ; Carson, Dennis A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c490t-192a962436d0fb731b15b2b6ffbc9bd8f9b74e9a7716c81ad84f0bb4feed8c2b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1986</creationdate><topic>Amino Acid Sequence</topic><topic>Amino acids</topic><topic>Antibodies</topic><topic>Antigens</topic><topic>Autoantibodies</topic><topic>Base Sequence</topic><topic>Biological and medical sciences</topic><topic>Complementary DNA</topic><topic>Cross Reactions</topic><topic>DNA - isolation & purification</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Fundamental immunology</topic><topic>Genes</topic><topic>Genetics of the immune response</topic><topic>Humans</topic><topic>Immunobiology</topic><topic>Immunoglobulin G - immunology</topic><topic>Immunoglobulin Idiotypes - genetics</topic><topic>Immunoglobulin kappa-Chains - genetics</topic><topic>Immunoglobulin M - immunology</topic><topic>Immunoglobulin Variable Region - genetics</topic><topic>Immunoglobulins</topic><topic>Libraries</topic><topic>Nucleotides</topic><topic>Rheumatoid Factor - genetics</topic><topic>Somatic mutation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chen, Pojen P.</creatorcontrib><creatorcontrib>Albrandt, Keith</creatorcontrib><creatorcontrib>Orida, Norman K.</creatorcontrib><creatorcontrib>Radoux, Victor</creatorcontrib><creatorcontrib>Chen, Emily Y.</creatorcontrib><creatorcontrib>Schrantz, Robert</creatorcontrib><creatorcontrib>Liu, Fu-Tong</creatorcontrib><creatorcontrib>Carson, Dennis A.</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chen, Pojen P.</au><au>Albrandt, Keith</au><au>Orida, Norman K.</au><au>Radoux, Victor</au><au>Chen, Emily Y.</au><au>Schrantz, Robert</au><au>Liu, Fu-Tong</au><au>Carson, Dennis A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Genetic Basis for the Cross-Reactive Idiotypes on the Light Chains of Human IgM Anti-IgG Autoantibodies</atitle><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle><addtitle>Proc Natl Acad Sci U S A</addtitle><date>1986-11-01</date><risdate>1986</risdate><volume>83</volume><issue>21</issue><spage>8318</spage><epage>8322</epage><pages>8318-8322</pages><issn>0027-8424</issn><eissn>1091-6490</eissn><coden>PNASA6</coden><abstract>The role of immunoglobulin structural genes in the generation of autoantibodies in humans has not been elucidated. Human monoclonal IgM anti-IgG autoantibodies (rheumatoid factors, RFs) from unrelated people often share idiotypic antigens. Antibodies against synthetic peptides have localized two of the shared idiotypic determinants to the second and third complementarity-determining regions of the κ light chain. The reported sequences of several human RF light chains are remarkably homologous in these regions. Animal studies have shown that some shared idiotypic antigens represent serological markers for immunoglobulin variable (V)-region genes. Therefore, we hypothesized that human RF light chains derived from a single germ-line gene, designated Vκ(RF) (RF), or from a small family of very closely related genes. In the present experiments, we have isolated and sequenced two human Vκgerm-line genes that encode κ light chains, which are identical or closely related to the light chains of human RF. The data indicate that the shared idiotypic antigens on RF are phenotypic markers for a κ V-region gene that is highly conserved in the human population. The results also imply that the light chains of IgM anti-IgG autoantibodies can be encoded by germ-line genes without any somatic mutation.</abstract><cop>Washington, DC</cop><pub>National Academy of Sciences of the United States of America</pub><pmid>3095834</pmid><doi>10.1073/pnas.83.21.8318</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; JSTOR Archive Collection A-Z Listing; PubMed Central; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry |
| subjects | Amino Acid Sequence Amino acids Antibodies Antigens Autoantibodies Base Sequence Biological and medical sciences Complementary DNA Cross Reactions DNA - isolation & purification Fundamental and applied biological sciences. Psychology Fundamental immunology Genes Genetics of the immune response Humans Immunobiology Immunoglobulin G - immunology Immunoglobulin Idiotypes - genetics Immunoglobulin kappa-Chains - genetics Immunoglobulin M - immunology Immunoglobulin Variable Region - genetics Immunoglobulins Libraries Nucleotides Rheumatoid Factor - genetics Somatic mutation |
| title | Genetic Basis for the Cross-Reactive Idiotypes on the Light Chains of Human IgM Anti-IgG Autoantibodies |
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