SAP is required for generating long-term humoral immunity
Long-lived plasma cells and memory B cells are the primary cellular components of long-term humoral immunity and as such are vitally important for the protection afforded by most vaccines. The SAP gene has been identified as the genetic locus responsible for X-linked lymphoproliferative disease, a f...
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| Veröffentlicht in: | Nature (London) 2003-01, Vol.421 (6920), p.282-287 |
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| creator | Crotty, Shane Kersh, Ellen N. Cannons, Jennifer Schwartzberg, Pamela L. Ahmed, Rafi |
| description | Long-lived plasma cells and memory B cells are the primary cellular components of long-term humoral immunity and as such are vitally important for the protection afforded by most vaccines. The
SAP
gene has been identified as the genetic locus responsible for X-linked lymphoproliferative disease, a fatal immunodeficiency
1
,
2
,
3
,
4
. Mutations in
SAP
have also been identified in some cases of severe common variable immunodeficiency disease
5
,
6
. The underlying cellular basis of this genetic disorder remains unclear. We have used a
SAP
knockout mouse model system to explore the role of SAP in immune responses. Here we report that mice lacking expression of SAP generate strong acute IgG antibody responses after viral infection, but show a near complete absence of virus-specific long-lived plasma cells and memory B cells, despite the presence of virus-specific memory CD4
+
T cells. Adoptive transfer experiments show that SAP-deficient B cells are normal and the defect is in CD4
+
T cells. Thus, SAP has a crucial role in CD4
+
T-cell function: it is essential for late B-cell help and the development of long-term humoral immunity but is not required for early B-cell help and class switching. |
| doi_str_mv | 10.1038/nature01318 |
| format | Article |
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SAP
gene has been identified as the genetic locus responsible for X-linked lymphoproliferative disease, a fatal immunodeficiency
1
,
2
,
3
,
4
. Mutations in
SAP
have also been identified in some cases of severe common variable immunodeficiency disease
5
,
6
. The underlying cellular basis of this genetic disorder remains unclear. We have used a
SAP
knockout mouse model system to explore the role of SAP in immune responses. Here we report that mice lacking expression of SAP generate strong acute IgG antibody responses after viral infection, but show a near complete absence of virus-specific long-lived plasma cells and memory B cells, despite the presence of virus-specific memory CD4
+
T cells. Adoptive transfer experiments show that SAP-deficient B cells are normal and the defect is in CD4
+
T cells. Thus, SAP has a crucial role in CD4
+
T-cell function: it is essential for late B-cell help and the development of long-term humoral immunity but is not required for early B-cell help and class switching.</description><identifier>ISSN: 0028-0836</identifier><identifier>EISSN: 1476-4687</identifier><identifier>DOI: 10.1038/nature01318</identifier><identifier>PMID: 12529646</identifier><identifier>CODEN: NATUAS</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>Adoptive Transfer ; Animals ; Antibody Formation - genetics ; Antibody Formation - immunology ; B-Lymphocytes - immunology ; Biological and medical sciences ; Carrier Proteins - genetics ; Carrier Proteins - physiology ; CD4-Positive T-Lymphocytes - immunology ; Cellular biology ; Flow Cytometry ; Fundamental and applied biological sciences. Psychology ; Fundamental immunology ; Genetics ; Humanities and Social Sciences ; Immune system ; Immunobiology ; Immunoglobulin G - immunology ; Immunologic Memory - genetics ; Immunologic Memory - immunology ; Intracellular Signaling Peptides and Proteins ; letter ; Lymphocytic choriomeningitis virus - immunology ; Lymphoid cells: ontogeny, maturation, markers, receptors, circulation and recirculation ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; multidisciplinary ; Plasma Cells - immunology ; Science ; Science (multidisciplinary) ; Signaling Lymphocytic Activation Molecule Associated Protein ; Time Factors</subject><ispartof>Nature (London), 2003-01, Vol.421 (6920), p.282-287</ispartof><rights>Macmillan Magazines Ltd. 2003</rights><rights>2003 INIST-CNRS</rights><rights>COPYRIGHT 2003 Nature Publishing Group</rights><rights>Copyright Macmillan Journals Ltd. Jan 16, 2003</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c644t-27dd0fd6e976e276bb685e487dec28024daf25284d468d3634629986dcb2b4e23</citedby><cites>FETCH-LOGICAL-c644t-27dd0fd6e976e276bb685e487dec28024daf25284d468d3634629986dcb2b4e23</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/nature01318$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/nature01318$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=14452208$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12529646$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Crotty, Shane</creatorcontrib><creatorcontrib>Kersh, Ellen N.</creatorcontrib><creatorcontrib>Cannons, Jennifer</creatorcontrib><creatorcontrib>Schwartzberg, Pamela L.</creatorcontrib><creatorcontrib>Ahmed, Rafi</creatorcontrib><title>SAP is required for generating long-term humoral immunity</title><title>Nature (London)</title><addtitle>Nature</addtitle><addtitle>Nature</addtitle><description>Long-lived plasma cells and memory B cells are the primary cellular components of long-term humoral immunity and as such are vitally important for the protection afforded by most vaccines. The
SAP
gene has been identified as the genetic locus responsible for X-linked lymphoproliferative disease, a fatal immunodeficiency
1
,
2
,
3
,
4
. Mutations in
SAP
have also been identified in some cases of severe common variable immunodeficiency disease
5
,
6
. The underlying cellular basis of this genetic disorder remains unclear. We have used a
SAP
knockout mouse model system to explore the role of SAP in immune responses. Here we report that mice lacking expression of SAP generate strong acute IgG antibody responses after viral infection, but show a near complete absence of virus-specific long-lived plasma cells and memory B cells, despite the presence of virus-specific memory CD4
+
T cells. Adoptive transfer experiments show that SAP-deficient B cells are normal and the defect is in CD4
+
T cells. Thus, SAP has a crucial role in CD4
+
T-cell function: it is essential for late B-cell help and the development of long-term humoral immunity but is not required for early B-cell help and class switching.</description><subject>Adoptive Transfer</subject><subject>Animals</subject><subject>Antibody Formation - genetics</subject><subject>Antibody Formation - immunology</subject><subject>B-Lymphocytes - immunology</subject><subject>Biological and medical sciences</subject><subject>Carrier Proteins - genetics</subject><subject>Carrier Proteins - physiology</subject><subject>CD4-Positive T-Lymphocytes - immunology</subject><subject>Cellular biology</subject><subject>Flow Cytometry</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Fundamental immunology</subject><subject>Genetics</subject><subject>Humanities and Social Sciences</subject><subject>Immune system</subject><subject>Immunobiology</subject><subject>Immunoglobulin G - immunology</subject><subject>Immunologic Memory - genetics</subject><subject>Immunologic Memory - immunology</subject><subject>Intracellular Signaling Peptides and Proteins</subject><subject>letter</subject><subject>Lymphocytic choriomeningitis virus - immunology</subject><subject>Lymphoid cells: ontogeny, maturation, markers, receptors, circulation and recirculation</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>multidisciplinary</subject><subject>Plasma Cells - immunology</subject><subject>Science</subject><subject>Science (multidisciplinary)</subject><subject>Signaling Lymphocytic Activation Molecule Associated Protein</subject><subject>Time Factors</subject><issn>0028-0836</issn><issn>1476-4687</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BEC</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqF0s-L1DAUB_AgijuunrxLWVER7ZqkaZIeh8EfC4uKu-IxpMlrzdKmM0kL7n9vhhmYHalKDoXkk2-Tl4fQU4LPCS7kO6_HKQAmBZH30IIwwXPGpbiPFhhTmWNZ8BP0KMYbjHFJBHuITggtacUZX6Dqavk1czELsJlcAJs1Q8ha8BD06HybdYNv8xFCn_2c-iHoLnN9P3k33j5GDxrdRXiy_56i7x_eX68-5ZdfPl6slpe54YyNORXW4sZyqAQHKnhdc1kCk8KCoRJTZnWTTiOZTYe2BS8Yp1UluTU1rRnQ4hS92uWuw7CZII6qd9FA12kPwxSVYGmLkLRM8uW_Zbozxbz4LySSc0oxS_DsD3gzTMGn66q0XJaCEZnQ8x1qdQfK-WYYgzbbRLUkUpRClnIblc-oXaVTkaFxafrIn814s3YbdRedz6A0LPTOzKa-PtqQzAi_xlZPMaqLq2_H9s3f7fL6x-rzrDZhiDFAo9bB9TrcKoLVtk_VnT5N-tm-sFPdgz3YfWMm8GIPdDS6a4L2xsWDY6xML7QNertzMS35FsLhheb--xtpHfic</recordid><startdate>20030116</startdate><enddate>20030116</enddate><creator>Crotty, Shane</creator><creator>Kersh, Ellen N.</creator><creator>Cannons, Jennifer</creator><creator>Schwartzberg, Pamela L.</creator><creator>Ahmed, Rafi</creator><general>Nature Publishing Group UK</general><general>Nature Publishing</general><general>Nature Publishing Group</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>ATWCN</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7ST</scope><scope>7T5</scope><scope>7TG</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88G</scope><scope>88I</scope><scope>8AF</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BEC</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>BKSAR</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M2M</scope><scope>M2O</scope><scope>M2P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>MBDVC</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PCBAR</scope><scope>PDBOC</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PSYQQ</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>Q9U</scope><scope>R05</scope><scope>RC3</scope><scope>S0X</scope><scope>SOI</scope><scope>7X8</scope><scope>7SC</scope><scope>7SP</scope><scope>7SR</scope><scope>7TB</scope><scope>7U5</scope><scope>8BQ</scope><scope>F28</scope><scope>JG9</scope><scope>JQ2</scope><scope>KR7</scope><scope>L7M</scope><scope>L~C</scope><scope>L~D</scope></search><sort><creationdate>20030116</creationdate><title>SAP is required for generating long-term humoral immunity</title><author>Crotty, Shane ; 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Psychology</topic><topic>Fundamental immunology</topic><topic>Genetics</topic><topic>Humanities and Social Sciences</topic><topic>Immune system</topic><topic>Immunobiology</topic><topic>Immunoglobulin G - immunology</topic><topic>Immunologic Memory - genetics</topic><topic>Immunologic Memory - immunology</topic><topic>Intracellular Signaling Peptides and Proteins</topic><topic>letter</topic><topic>Lymphocytic choriomeningitis virus - immunology</topic><topic>Lymphoid cells: ontogeny, maturation, markers, receptors, circulation and recirculation</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Knockout</topic><topic>multidisciplinary</topic><topic>Plasma Cells - immunology</topic><topic>Science</topic><topic>Science (multidisciplinary)</topic><topic>Signaling Lymphocytic Activation Molecule Associated Protein</topic><topic>Time Factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Crotty, Shane</creatorcontrib><creatorcontrib>Kersh, Ellen N.</creatorcontrib><creatorcontrib>Cannons, Jennifer</creatorcontrib><creatorcontrib>Schwartzberg, Pamela L.</creatorcontrib><creatorcontrib>Ahmed, Rafi</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>Gale In Context: Middle School</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Environment Abstracts</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical 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>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Psychology Database (Alumni)</collection><collection>Science Database (Alumni Edition)</collection><collection>STEM Database</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>eLibrary</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Earth, Atmospheric & Aquatic Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - 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The
SAP
gene has been identified as the genetic locus responsible for X-linked lymphoproliferative disease, a fatal immunodeficiency
1
,
2
,
3
,
4
. Mutations in
SAP
have also been identified in some cases of severe common variable immunodeficiency disease
5
,
6
. The underlying cellular basis of this genetic disorder remains unclear. We have used a
SAP
knockout mouse model system to explore the role of SAP in immune responses. Here we report that mice lacking expression of SAP generate strong acute IgG antibody responses after viral infection, but show a near complete absence of virus-specific long-lived plasma cells and memory B cells, despite the presence of virus-specific memory CD4
+
T cells. Adoptive transfer experiments show that SAP-deficient B cells are normal and the defect is in CD4
+
T cells. Thus, SAP has a crucial role in CD4
+
T-cell function: it is essential for late B-cell help and the development of long-term humoral immunity but is not required for early B-cell help and class switching.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>12529646</pmid><doi>10.1038/nature01318</doi><tpages>6</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0028-0836 |
| ispartof | Nature (London), 2003-01, Vol.421 (6920), p.282-287 |
| issn | 0028-0836 1476-4687 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_743467825 |
| source | MEDLINE; Springer Nature - Complete Springer Journals; Nature Journals Online |
| subjects | Adoptive Transfer Animals Antibody Formation - genetics Antibody Formation - immunology B-Lymphocytes - immunology Biological and medical sciences Carrier Proteins - genetics Carrier Proteins - physiology CD4-Positive T-Lymphocytes - immunology Cellular biology Flow Cytometry Fundamental and applied biological sciences. Psychology Fundamental immunology Genetics Humanities and Social Sciences Immune system Immunobiology Immunoglobulin G - immunology Immunologic Memory - genetics Immunologic Memory - immunology Intracellular Signaling Peptides and Proteins letter Lymphocytic choriomeningitis virus - immunology Lymphoid cells: ontogeny, maturation, markers, receptors, circulation and recirculation Male Mice Mice, Inbred C57BL Mice, Knockout multidisciplinary Plasma Cells - immunology Science Science (multidisciplinary) Signaling Lymphocytic Activation Molecule Associated Protein Time Factors |
| title | SAP is required for generating long-term humoral immunity |
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