Inhibition of Thymocyte Apoptosis and Negative Antigenic Selection in bcl-2 Transgenic Mice
The bcl-2 gene, which is overexpressed in human follicular B-cell lymphomas, has been found to extend cellular lifespan through inhibition of apoptosis, or programmed cell death. However, the physiological role of the Bcl-2 protein in lymphocyte development is unclear. We have established a transgen...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 1992-08, Vol.89 (15), p.7003-7007 |
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| container_title | Proceedings of the National Academy of Sciences - PNAS |
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| creator | Siegel, Richard M. Katsumata, Makoto Miyashita, Toshiyuki Louie, Diane C. Greene, Mark I. Reed, John C. |
| description | The bcl-2 gene, which is overexpressed in human follicular B-cell lymphomas, has been found to extend cellular lifespan through inhibition of apoptosis, or programmed cell death. However, the physiological role of the Bcl-2 protein in lymphocyte development is unclear. We have established a transgenic mouse line that expresses high levels of the Bcl-2 protein in both cortical and medullary thymocytes, disrupting the normal pattern of expression of this gene. We found that in these mice, immature thymocytes became resistant to apoptosis mediated by corticosteroids and calcium ionophores. Untreated thymocytes also exhibited a survival advantage in suspension cultures compared with controls. In addition, overexpression of bcl-2 enabled a proportion of thymocytes and peripheral T cells to escape the process of clonal deletion, which normally eliminates self-reactive T cells during thymocyte maturation. These findings implicate the Bcl-2 protein in regulating the lifespan of maturing thymocytes and in the antigenic-selection process. |
| doi_str_mv | 10.1073/pnas.89.15.7003 |
| format | Article |
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However, the physiological role of the Bcl-2 protein in lymphocyte development is unclear. We have established a transgenic mouse line that expresses high levels of the Bcl-2 protein in both cortical and medullary thymocytes, disrupting the normal pattern of expression of this gene. We found that in these mice, immature thymocytes became resistant to apoptosis mediated by corticosteroids and calcium ionophores. Untreated thymocytes also exhibited a survival advantage in suspension cultures compared with controls. In addition, overexpression of bcl-2 enabled a proportion of thymocytes and peripheral T cells to escape the process of clonal deletion, which normally eliminates self-reactive T cells during thymocyte maturation. These findings implicate the Bcl-2 protein in regulating the lifespan of maturing thymocytes and in the antigenic-selection process.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.89.15.7003</identifier><identifier>PMID: 1495993</identifier><identifier>CODEN: PNASA6</identifier><language>eng</language><publisher>Washington, DC: National Academy of Sciences of the United States of America</publisher><subject>Animals ; Antigens - immunology ; Apoptosis ; Biological and medical sciences ; Cell Death ; Cell lines ; Chromosomes, Human, Pair 14 ; Chromosomes, Human, Pair 18 ; Clonal deletion ; Crosses, Genetic ; Dexamethasone - pharmacology ; Enhancer Elements, Genetic ; Fundamental and applied biological sciences. Psychology ; Fundamental immunology ; Genetics ; Humans ; Immunobiology ; Immunoglobulin Heavy Chains - genetics ; Immunoglobulin Variable Region - genetics ; Immunophenotyping ; Lymph nodes ; Lymphoid cells: ontogeny, maturation, markers, receptors, circulation and recirculation ; Mice ; Mice, Inbred Strains ; Mice, Transgenic ; Proteins ; Proto-Oncogene Proteins - genetics ; Proto-Oncogene Proteins c-bcl-2 ; Proto-Oncogenes ; Rodents ; T lymphocytes ; T-Lymphocyte Subsets - cytology ; T-Lymphocyte Subsets - immunology ; T-Lymphocytes - cytology ; T-Lymphocytes - drug effects ; T-Lymphocytes - immunology ; Thymocytes ; Transgenes ; Transgenic animals</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 1992-08, Vol.89 (15), p.7003-7007</ispartof><rights>Copyright 1992 The National Academy of Sciences of the United States of America</rights><rights>1992 INIST-CNRS</rights><rights>Copyright National Academy of Sciences Aug 1, 1992</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c615t-2d8480d7e8f852a78c187e62df1d26185bae8436e52a60b19c6fce9ba0408b213</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/89/15.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/2359919$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/2359919$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,727,780,784,803,885,27924,27925,53791,53793,58017,58250</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=5494273$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/1495993$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Siegel, Richard M.</creatorcontrib><creatorcontrib>Katsumata, Makoto</creatorcontrib><creatorcontrib>Miyashita, Toshiyuki</creatorcontrib><creatorcontrib>Louie, Diane C.</creatorcontrib><creatorcontrib>Greene, Mark I.</creatorcontrib><creatorcontrib>Reed, John C.</creatorcontrib><title>Inhibition of Thymocyte Apoptosis and Negative Antigenic Selection in bcl-2 Transgenic Mice</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>The bcl-2 gene, which is overexpressed in human follicular B-cell lymphomas, has been found to extend cellular lifespan through inhibition of apoptosis, or programmed cell death. However, the physiological role of the Bcl-2 protein in lymphocyte development is unclear. We have established a transgenic mouse line that expresses high levels of the Bcl-2 protein in both cortical and medullary thymocytes, disrupting the normal pattern of expression of this gene. We found that in these mice, immature thymocytes became resistant to apoptosis mediated by corticosteroids and calcium ionophores. Untreated thymocytes also exhibited a survival advantage in suspension cultures compared with controls. In addition, overexpression of bcl-2 enabled a proportion of thymocytes and peripheral T cells to escape the process of clonal deletion, which normally eliminates self-reactive T cells during thymocyte maturation. These findings implicate the Bcl-2 protein in regulating the lifespan of maturing thymocytes and in the antigenic-selection process.</description><subject>Animals</subject><subject>Antigens - immunology</subject><subject>Apoptosis</subject><subject>Biological and medical sciences</subject><subject>Cell Death</subject><subject>Cell lines</subject><subject>Chromosomes, Human, Pair 14</subject><subject>Chromosomes, Human, Pair 18</subject><subject>Clonal deletion</subject><subject>Crosses, Genetic</subject><subject>Dexamethasone - pharmacology</subject><subject>Enhancer Elements, Genetic</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Fundamental immunology</subject><subject>Genetics</subject><subject>Humans</subject><subject>Immunobiology</subject><subject>Immunoglobulin Heavy Chains - genetics</subject><subject>Immunoglobulin Variable Region - genetics</subject><subject>Immunophenotyping</subject><subject>Lymph nodes</subject><subject>Lymphoid cells: ontogeny, maturation, markers, receptors, circulation and recirculation</subject><subject>Mice</subject><subject>Mice, Inbred Strains</subject><subject>Mice, Transgenic</subject><subject>Proteins</subject><subject>Proto-Oncogene Proteins - genetics</subject><subject>Proto-Oncogene Proteins c-bcl-2</subject><subject>Proto-Oncogenes</subject><subject>Rodents</subject><subject>T lymphocytes</subject><subject>T-Lymphocyte Subsets - cytology</subject><subject>T-Lymphocyte Subsets - immunology</subject><subject>T-Lymphocytes - cytology</subject><subject>T-Lymphocytes - drug effects</subject><subject>T-Lymphocytes - immunology</subject><subject>Thymocytes</subject><subject>Transgenes</subject><subject>Transgenic animals</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1992</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc9v0zAcxS0EGl3hzAVQNCE4pfOv-IfEZZqATRpwoJw4WI7jtK5SO8TORP97XFLKxgHkgyW_z_v62Q-AZwguEOTkvPc6LoRcoGrBISQPwAxBiUpGJXwIZhBiXgqK6WNwGuMGQigrAU_ACaKykpLMwLdrv3a1Sy74IrTFcr3bBrNLtrjoQ59CdLHQvik-2ZVO7jYf--RW1jtTfLGdNb98zhe16UpcLAft46R-dMY-AY9a3UX79LDPwdf375aXV-XN5w_Xlxc3pWGoSiVuBBWw4Va0osKaC4MEtww3LWowQ6KqtRWUMJtFBmskDWuNlbWGFIoaIzIHb6e5_VhvbWOsT4PuVD-4rR52Kmin7iverdUq3CoqGSHZ_vpgH8L30cakti4a23Xa2zBGxQlCTFT_BxHDnMi85uDsL3ATxsHnP1AYIiw4FyxD5xNkhhDjYNtjYATVvlu171YJqVCl9t1mx4u77_zDT2Vm_dVB19Hors1tGBePWEUlzQEz9vKA7ef_Vu_d8-afgGrHrkv2R8rk84ncxBSGI4pJzoMk-Qkxb85M</recordid><startdate>19920801</startdate><enddate>19920801</enddate><creator>Siegel, Richard M.</creator><creator>Katsumata, Makoto</creator><creator>Miyashita, Toshiyuki</creator><creator>Louie, Diane C.</creator><creator>Greene, Mark I.</creator><creator>Reed, John C.</creator><general>National Academy of Sciences of the United States of America</general><general>National Acad Sciences</general><general>National Academy of 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>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>19920801</creationdate><title>Inhibition of Thymocyte Apoptosis and Negative Antigenic Selection in bcl-2 Transgenic Mice</title><author>Siegel, Richard M. ; Katsumata, Makoto ; Miyashita, Toshiyuki ; Louie, Diane C. ; Greene, Mark I. ; Reed, John C.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c615t-2d8480d7e8f852a78c187e62df1d26185bae8436e52a60b19c6fce9ba0408b213</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1992</creationdate><topic>Animals</topic><topic>Antigens - immunology</topic><topic>Apoptosis</topic><topic>Biological and medical sciences</topic><topic>Cell Death</topic><topic>Cell lines</topic><topic>Chromosomes, Human, Pair 14</topic><topic>Chromosomes, Human, Pair 18</topic><topic>Clonal deletion</topic><topic>Crosses, Genetic</topic><topic>Dexamethasone - pharmacology</topic><topic>Enhancer Elements, Genetic</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Fundamental immunology</topic><topic>Genetics</topic><topic>Humans</topic><topic>Immunobiology</topic><topic>Immunoglobulin Heavy Chains - genetics</topic><topic>Immunoglobulin Variable Region - genetics</topic><topic>Immunophenotyping</topic><topic>Lymph nodes</topic><topic>Lymphoid cells: ontogeny, maturation, markers, receptors, circulation and recirculation</topic><topic>Mice</topic><topic>Mice, Inbred Strains</topic><topic>Mice, Transgenic</topic><topic>Proteins</topic><topic>Proto-Oncogene Proteins - genetics</topic><topic>Proto-Oncogene Proteins c-bcl-2</topic><topic>Proto-Oncogenes</topic><topic>Rodents</topic><topic>T lymphocytes</topic><topic>T-Lymphocyte Subsets - cytology</topic><topic>T-Lymphocyte Subsets - immunology</topic><topic>T-Lymphocytes - cytology</topic><topic>T-Lymphocytes - drug effects</topic><topic>T-Lymphocytes - immunology</topic><topic>Thymocytes</topic><topic>Transgenes</topic><topic>Transgenic animals</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Siegel, Richard M.</creatorcontrib><creatorcontrib>Katsumata, Makoto</creatorcontrib><creatorcontrib>Miyashita, Toshiyuki</creatorcontrib><creatorcontrib>Louie, Diane C.</creatorcontrib><creatorcontrib>Greene, Mark I.</creatorcontrib><creatorcontrib>Reed, John C.</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>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors 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>Genetics Abstracts</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>Siegel, Richard M.</au><au>Katsumata, Makoto</au><au>Miyashita, Toshiyuki</au><au>Louie, Diane C.</au><au>Greene, Mark I.</au><au>Reed, John C.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Inhibition of Thymocyte Apoptosis and Negative Antigenic Selection in bcl-2 Transgenic Mice</atitle><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle><addtitle>Proc Natl Acad Sci U S A</addtitle><date>1992-08-01</date><risdate>1992</risdate><volume>89</volume><issue>15</issue><spage>7003</spage><epage>7007</epage><pages>7003-7007</pages><issn>0027-8424</issn><eissn>1091-6490</eissn><coden>PNASA6</coden><abstract>The bcl-2 gene, which is overexpressed in human follicular B-cell lymphomas, has been found to extend cellular lifespan through inhibition of apoptosis, or programmed cell death. However, the physiological role of the Bcl-2 protein in lymphocyte development is unclear. We have established a transgenic mouse line that expresses high levels of the Bcl-2 protein in both cortical and medullary thymocytes, disrupting the normal pattern of expression of this gene. We found that in these mice, immature thymocytes became resistant to apoptosis mediated by corticosteroids and calcium ionophores. Untreated thymocytes also exhibited a survival advantage in suspension cultures compared with controls. In addition, overexpression of bcl-2 enabled a proportion of thymocytes and peripheral T cells to escape the process of clonal deletion, which normally eliminates self-reactive T cells during thymocyte maturation. These findings implicate the Bcl-2 protein in regulating the lifespan of maturing thymocytes and in the antigenic-selection process.</abstract><cop>Washington, DC</cop><pub>National Academy of Sciences of the United States of America</pub><pmid>1495993</pmid><doi>10.1073/pnas.89.15.7003</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Proceedings of the National Academy of Sciences - PNAS, 1992-08, Vol.89 (15), p.7003-7007 |
| issn | 0027-8424 1091-6490 |
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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 | Animals Antigens - immunology Apoptosis Biological and medical sciences Cell Death Cell lines Chromosomes, Human, Pair 14 Chromosomes, Human, Pair 18 Clonal deletion Crosses, Genetic Dexamethasone - pharmacology Enhancer Elements, Genetic Fundamental and applied biological sciences. Psychology Fundamental immunology Genetics Humans Immunobiology Immunoglobulin Heavy Chains - genetics Immunoglobulin Variable Region - genetics Immunophenotyping Lymph nodes Lymphoid cells: ontogeny, maturation, markers, receptors, circulation and recirculation Mice Mice, Inbred Strains Mice, Transgenic Proteins Proto-Oncogene Proteins - genetics Proto-Oncogene Proteins c-bcl-2 Proto-Oncogenes Rodents T lymphocytes T-Lymphocyte Subsets - cytology T-Lymphocyte Subsets - immunology T-Lymphocytes - cytology T-Lymphocytes - drug effects T-Lymphocytes - immunology Thymocytes Transgenes Transgenic animals |
| title | Inhibition of Thymocyte Apoptosis and Negative Antigenic Selection in bcl-2 Transgenic Mice |
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