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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">IL-21 signalling via STAT3 primes human naïve B cells to respond to IL-2 to enhance their differentiation into plasmablasts</title><author><name sortKey="Berglund, Lucinda J" sort="Berglund, Lucinda J" uniqKey="Berglund L" first="Lucinda J." last="Berglund">Lucinda J. Berglund</name><affiliation><nlm:aff id="aff1">Immunology Research Program, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia;</nlm:aff></affiliation><affiliation><nlm:aff id="aff2">St Vincent’s Clinical School, University of New South Wales, Australia;</nlm:aff></affiliation><affiliation><nlm:aff id="aff3">Department of Immunology, Institute of Clinical Pathology and Medical Research, Westmead Hospital, Westmead, NSW, Australia;</nlm:aff></affiliation></author><author><name sortKey="Avery, Danielle T" sort="Avery, Danielle T" uniqKey="Avery D" first="Danielle T." last="Avery">Danielle T. Avery</name><affiliation><nlm:aff id="aff1">Immunology Research Program, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia;</nlm:aff></affiliation></author><author><name sortKey="Ma, Cindy S" sort="Ma, Cindy S" uniqKey="Ma C" first="Cindy S." last="Ma">Cindy S. Ma</name><affiliation><nlm:aff id="aff1">Immunology Research Program, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia;</nlm:aff></affiliation><affiliation><nlm:aff id="aff2">St Vincent’s Clinical School, University of New South Wales, Australia;</nlm:aff></affiliation></author><author><name sortKey="Moens, Leen" sort="Moens, Leen" uniqKey="Moens L" first="Leen" last="Moens">Leen Moens</name><affiliation><nlm:aff id="aff1">Immunology Research Program, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia;</nlm:aff></affiliation></author><author><name sortKey="Deenick, Elissa K" sort="Deenick, Elissa K" uniqKey="Deenick E" first="Elissa K." last="Deenick">Elissa K. Deenick</name><affiliation><nlm:aff id="aff1">Immunology Research Program, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia;</nlm:aff></affiliation><affiliation><nlm:aff id="aff2">St Vincent’s Clinical School, University of New South Wales, Australia;</nlm:aff></affiliation></author><author><name sortKey="Bustamante, Jacinta" sort="Bustamante, Jacinta" uniqKey="Bustamante J" first="Jacinta" last="Bustamante">Jacinta Bustamante</name><affiliation><nlm:aff id="aff4">Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U980, Necker Medical School, University Paris Descartes, Paris, France;</nlm:aff></affiliation><affiliation><nlm:aff id="aff5">Study Center for Primary Immunodeficiencies, AP-HP, Necker Hospital, Paris, France;</nlm:aff></affiliation><affiliation><nlm:aff id="aff6">Université Paris Descartes, Institut Imagine, Paris, France;</nlm:aff></affiliation></author><author><name sortKey="Boisson Dupuis, Stephanie" sort="Boisson Dupuis, Stephanie" uniqKey="Boisson Dupuis S" first="Stephanie" last="Boisson-Dupuis">Stephanie Boisson-Dupuis</name><affiliation><nlm:aff id="aff4">Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U980, Necker Medical School, University Paris Descartes, Paris, France;</nlm:aff></affiliation><affiliation><nlm:aff id="aff7">Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY;</nlm:aff></affiliation></author><author><name sortKey="Wong, Melanie" sort="Wong, Melanie" uniqKey="Wong M" first="Melanie" last="Wong">Melanie Wong</name><affiliation><nlm:aff id="aff8">Department of Immunology, Children’s Hospital at Westmead, Westmead, NSW, Australia;</nlm:aff></affiliation></author><author><name sortKey="Adelstein, Stephen" sort="Adelstein, Stephen" uniqKey="Adelstein S" first="Stephen" last="Adelstein">Stephen Adelstein</name><affiliation><nlm:aff id="aff9">Clinical Immunology, Royal Prince Alfred Hospital, Sydney, NSW, Australia;</nlm:aff></affiliation></author><author><name sortKey="Arkwright, Peter D" sort="Arkwright, Peter D" uniqKey="Arkwright P" first="Peter D." last="Arkwright">Peter D. Arkwright</name><affiliation><nlm:aff id="aff10">University of Manchester, Royal Manchester Children’s Hospital, Manchester, United Kingdom;</nlm:aff></affiliation></author><author><name sortKey="Bacchetta, Rosa" sort="Bacchetta, Rosa" uniqKey="Bacchetta R" first="Rosa" last="Bacchetta">Rosa Bacchetta</name><affiliation><nlm:aff id="aff11">San Raffaele Telethon Institute for Gene Therapy (HSR-TIGET), San Raffaele Scientific Institute, Milan, Italy;</nlm:aff></affiliation></author><author><name sortKey="Bezrodnik, Liliana" sort="Bezrodnik, Liliana" uniqKey="Bezrodnik L" first="Liliana" last="Bezrodnik">Liliana Bezrodnik</name><affiliation><nlm:aff id="aff12">Immunology Unit, Ricardo Gutiérrez Children Hosptial, Ciudad Autónoma de Buenos Aires, Argentina;</nlm:aff></affiliation></author><author><name sortKey="Dadi, Harjit" sort="Dadi, Harjit" uniqKey="Dadi H" first="Harjit" last="Dadi">Harjit Dadi</name><affiliation><nlm:aff id="aff13">Canadian Centre for Primary Immunodeficiency, Hospital for Sick Children and University of Toronto, Toronto, ON, Canada;</nlm:aff></affiliation></author><author><name sortKey="Roifman, Chaim M" sort="Roifman, Chaim M" uniqKey="Roifman C" first="Chaim M." last="Roifman">Chaim M. Roifman</name><affiliation><nlm:aff id="aff13">Canadian Centre for Primary Immunodeficiency, Hospital for Sick Children and University of Toronto, Toronto, ON, Canada;</nlm:aff></affiliation></author><author><name sortKey="Fulcher, David A" sort="Fulcher, David A" uniqKey="Fulcher D" first="David A." last="Fulcher">David A. Fulcher</name><affiliation><nlm:aff id="aff3">Department of Immunology, Institute of Clinical Pathology and Medical Research, Westmead Hospital, Westmead, NSW, Australia;</nlm:aff></affiliation></author><author><name sortKey="Ziegler, John B" sort="Ziegler, John B" uniqKey="Ziegler J" first="John B." last="Ziegler">John B. Ziegler</name><affiliation><nlm:aff id="aff14">Department of Immunology, Sydney Children's Hospital, Randwick, NSW, Australia and School of Women’s and Children’s Health, University of NSW, Randwick, Australia;</nlm:aff></affiliation></author><author><name sortKey="Smart, Joanne M" sort="Smart, Joanne M" uniqKey="Smart J" first="Joanne M." last="Smart">Joanne M. Smart</name><affiliation><nlm:aff id="aff15">Department of Allergy and Immunology, Royal Children’s Hospital Melbourne, Melbourne, VIC, Australia;</nlm:aff></affiliation></author><author><name sortKey="Kobayashi, Masao" sort="Kobayashi, Masao" uniqKey="Kobayashi M" first="Masao" last="Kobayashi">Masao Kobayashi</name><affiliation><nlm:aff id="aff16">Department of Pediatrics, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, Japan;</nlm:aff></affiliation></author><author><name sortKey="Picard, Capucine" sort="Picard, Capucine" uniqKey="Picard C" first="Capucine" last="Picard">Capucine Picard</name><affiliation><nlm:aff id="aff4">Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U980, Necker Medical School, University Paris Descartes, Paris, France;</nlm:aff></affiliation><affiliation><nlm:aff id="aff5">Study Center for Primary Immunodeficiencies, AP-HP, Necker Hospital, Paris, France;</nlm:aff></affiliation><affiliation><nlm:aff id="aff6">Université Paris Descartes, Institut Imagine, Paris, France;</nlm:aff></affiliation></author><author><name sortKey="Durandy, Anne" sort="Durandy, Anne" uniqKey="Durandy A" first="Anne" last="Durandy">Anne Durandy</name><affiliation><nlm:aff id="aff5">Study Center for Primary Immunodeficiencies, AP-HP, Necker Hospital, Paris, France;</nlm:aff></affiliation><affiliation><nlm:aff id="aff6">Université Paris Descartes, Institut Imagine, Paris, France;</nlm:aff></affiliation><affiliation><nlm:aff id="aff17">INSERM, Unité U768, Hôpital Necker Enfants-Malades, Paris, France;</nlm:aff></affiliation></author><author><name sortKey="Cook, Matthew C" sort="Cook, Matthew C" uniqKey="Cook M" first="Matthew C." last="Cook">Matthew C. Cook</name><affiliation><nlm:aff wicri:cut=", and" id="aff18">Australian National University Medical School</nlm:aff></affiliation><affiliation><nlm:aff id="aff19">John Curtin School of Medical Research, Australian National University, ACT, Canberra, Australia;</nlm:aff></affiliation><affiliation><nlm:aff wicri:cut="; and" id="aff20">Department of Immunology, The Canberra Hospital, Canberra, ACT, Australia</nlm:aff></affiliation></author><author><name sortKey="Casanova, Jean Laurent" sort="Casanova, Jean Laurent" uniqKey="Casanova J" first="Jean-Laurent" last="Casanova">Jean-Laurent Casanova</name><affiliation><nlm:aff id="aff4">Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U980, Necker Medical School, University Paris Descartes, Paris, France;</nlm:aff></affiliation><affiliation><nlm:aff id="aff6">Université Paris Descartes, Institut Imagine, Paris, France;</nlm:aff></affiliation><affiliation><nlm:aff id="aff7">Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY;</nlm:aff></affiliation></author><author><name sortKey="Uzel, Gulbu" sort="Uzel, Gulbu" uniqKey="Uzel G" first="Gulbu" last="Uzel">Gulbu Uzel</name><affiliation><nlm:aff id="aff21">Immunopathogenesis Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD</nlm:aff></affiliation></author><author><name sortKey="Tangye, Stuart G" sort="Tangye, Stuart G" uniqKey="Tangye S" first="Stuart G." last="Tangye">Stuart G. Tangye</name><affiliation><nlm:aff id="aff1">Immunology Research Program, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia;</nlm:aff></affiliation><affiliation><nlm:aff id="aff2">St Vincent’s Clinical School, University of New South Wales, Australia;</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">24159173</idno><idno type="pmc">3854113</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3854113</idno><idno type="RBID">PMC:3854113</idno><idno type="doi">10.1182/blood-2013-06-506865</idno><date when="2013">2013</date><idno type="wicri:Area/Pmc/Corpus">001801</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">001801</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">IL-21 signalling via STAT3 primes human naïve B cells to respond to IL-2 to enhance their differentiation into plasmablasts</title><author><name sortKey="Berglund, Lucinda J" sort="Berglund, Lucinda J" uniqKey="Berglund L" first="Lucinda J." last="Berglund">Lucinda J. Berglund</name><affiliation><nlm:aff id="aff1">Immunology Research Program, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia;</nlm:aff></affiliation><affiliation><nlm:aff id="aff2">St Vincent’s Clinical School, University of New South Wales, Australia;</nlm:aff></affiliation><affiliation><nlm:aff id="aff3">Department of Immunology, Institute of Clinical Pathology and Medical Research, Westmead Hospital, Westmead, NSW, Australia;</nlm:aff></affiliation></author><author><name sortKey="Avery, Danielle T" sort="Avery, Danielle T" uniqKey="Avery D" first="Danielle T." last="Avery">Danielle T. Avery</name><affiliation><nlm:aff id="aff1">Immunology Research Program, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia;</nlm:aff></affiliation></author><author><name sortKey="Ma, Cindy S" sort="Ma, Cindy S" uniqKey="Ma C" first="Cindy S." last="Ma">Cindy S. Ma</name><affiliation><nlm:aff id="aff1">Immunology Research Program, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia;</nlm:aff></affiliation><affiliation><nlm:aff id="aff2">St Vincent’s Clinical School, University of New South Wales, Australia;</nlm:aff></affiliation></author><author><name sortKey="Moens, Leen" sort="Moens, Leen" uniqKey="Moens L" first="Leen" last="Moens">Leen Moens</name><affiliation><nlm:aff id="aff1">Immunology Research Program, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia;</nlm:aff></affiliation></author><author><name sortKey="Deenick, Elissa K" sort="Deenick, Elissa K" uniqKey="Deenick E" first="Elissa K." last="Deenick">Elissa K. Deenick</name><affiliation><nlm:aff id="aff1">Immunology Research Program, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia;</nlm:aff></affiliation><affiliation><nlm:aff id="aff2">St Vincent’s Clinical School, University of New South Wales, Australia;</nlm:aff></affiliation></author><author><name sortKey="Bustamante, Jacinta" sort="Bustamante, Jacinta" uniqKey="Bustamante J" first="Jacinta" last="Bustamante">Jacinta Bustamante</name><affiliation><nlm:aff id="aff4">Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U980, Necker Medical School, University Paris Descartes, Paris, France;</nlm:aff></affiliation><affiliation><nlm:aff id="aff5">Study Center for Primary Immunodeficiencies, AP-HP, Necker Hospital, Paris, France;</nlm:aff></affiliation><affiliation><nlm:aff id="aff6">Université Paris Descartes, Institut Imagine, Paris, France;</nlm:aff></affiliation></author><author><name sortKey="Boisson Dupuis, Stephanie" sort="Boisson Dupuis, Stephanie" uniqKey="Boisson Dupuis S" first="Stephanie" last="Boisson-Dupuis">Stephanie Boisson-Dupuis</name><affiliation><nlm:aff id="aff4">Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U980, Necker Medical School, University Paris Descartes, Paris, France;</nlm:aff></affiliation><affiliation><nlm:aff id="aff7">Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY;</nlm:aff></affiliation></author><author><name sortKey="Wong, Melanie" sort="Wong, Melanie" uniqKey="Wong M" first="Melanie" last="Wong">Melanie Wong</name><affiliation><nlm:aff id="aff8">Department of Immunology, Children’s Hospital at Westmead, Westmead, NSW, Australia;</nlm:aff></affiliation></author><author><name sortKey="Adelstein, Stephen" sort="Adelstein, Stephen" uniqKey="Adelstein S" first="Stephen" last="Adelstein">Stephen Adelstein</name><affiliation><nlm:aff id="aff9">Clinical Immunology, Royal Prince Alfred Hospital, Sydney, NSW, Australia;</nlm:aff></affiliation></author><author><name sortKey="Arkwright, Peter D" sort="Arkwright, Peter D" uniqKey="Arkwright P" first="Peter D." last="Arkwright">Peter D. Arkwright</name><affiliation><nlm:aff id="aff10">University of Manchester, Royal Manchester Children’s Hospital, Manchester, United Kingdom;</nlm:aff></affiliation></author><author><name sortKey="Bacchetta, Rosa" sort="Bacchetta, Rosa" uniqKey="Bacchetta R" first="Rosa" last="Bacchetta">Rosa Bacchetta</name><affiliation><nlm:aff id="aff11">San Raffaele Telethon Institute for Gene Therapy (HSR-TIGET), San Raffaele Scientific Institute, Milan, Italy;</nlm:aff></affiliation></author><author><name sortKey="Bezrodnik, Liliana" sort="Bezrodnik, Liliana" uniqKey="Bezrodnik L" first="Liliana" last="Bezrodnik">Liliana Bezrodnik</name><affiliation><nlm:aff id="aff12">Immunology Unit, Ricardo Gutiérrez Children Hosptial, Ciudad Autónoma de Buenos Aires, Argentina;</nlm:aff></affiliation></author><author><name sortKey="Dadi, Harjit" sort="Dadi, Harjit" uniqKey="Dadi H" first="Harjit" last="Dadi">Harjit Dadi</name><affiliation><nlm:aff id="aff13">Canadian Centre for Primary Immunodeficiency, Hospital for Sick Children and University of Toronto, Toronto, ON, Canada;</nlm:aff></affiliation></author><author><name sortKey="Roifman, Chaim M" sort="Roifman, Chaim M" uniqKey="Roifman C" first="Chaim M." last="Roifman">Chaim M. Roifman</name><affiliation><nlm:aff id="aff13">Canadian Centre for Primary Immunodeficiency, Hospital for Sick Children and University of Toronto, Toronto, ON, Canada;</nlm:aff></affiliation></author><author><name sortKey="Fulcher, David A" sort="Fulcher, David A" uniqKey="Fulcher D" first="David A." last="Fulcher">David A. Fulcher</name><affiliation><nlm:aff id="aff3">Department of Immunology, Institute of Clinical Pathology and Medical Research, Westmead Hospital, Westmead, NSW, Australia;</nlm:aff></affiliation></author><author><name sortKey="Ziegler, John B" sort="Ziegler, John B" uniqKey="Ziegler J" first="John B." last="Ziegler">John B. Ziegler</name><affiliation><nlm:aff id="aff14">Department of Immunology, Sydney Children's Hospital, Randwick, NSW, Australia and School of Women’s and Children’s Health, University of NSW, Randwick, Australia;</nlm:aff></affiliation></author><author><name sortKey="Smart, Joanne M" sort="Smart, Joanne M" uniqKey="Smart J" first="Joanne M." last="Smart">Joanne M. Smart</name><affiliation><nlm:aff id="aff15">Department of Allergy and Immunology, Royal Children’s Hospital Melbourne, Melbourne, VIC, Australia;</nlm:aff></affiliation></author><author><name sortKey="Kobayashi, Masao" sort="Kobayashi, Masao" uniqKey="Kobayashi M" first="Masao" last="Kobayashi">Masao Kobayashi</name><affiliation><nlm:aff id="aff16">Department of Pediatrics, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, Japan;</nlm:aff></affiliation></author><author><name sortKey="Picard, Capucine" sort="Picard, Capucine" uniqKey="Picard C" first="Capucine" last="Picard">Capucine Picard</name><affiliation><nlm:aff id="aff4">Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U980, Necker Medical School, University Paris Descartes, Paris, France;</nlm:aff></affiliation><affiliation><nlm:aff id="aff5">Study Center for Primary Immunodeficiencies, AP-HP, Necker Hospital, Paris, France;</nlm:aff></affiliation><affiliation><nlm:aff id="aff6">Université Paris Descartes, Institut Imagine, Paris, France;</nlm:aff></affiliation></author><author><name sortKey="Durandy, Anne" sort="Durandy, Anne" uniqKey="Durandy A" first="Anne" last="Durandy">Anne Durandy</name><affiliation><nlm:aff id="aff5">Study Center for Primary Immunodeficiencies, AP-HP, Necker Hospital, Paris, France;</nlm:aff></affiliation><affiliation><nlm:aff id="aff6">Université Paris Descartes, Institut Imagine, Paris, France;</nlm:aff></affiliation><affiliation><nlm:aff id="aff17">INSERM, Unité U768, Hôpital Necker Enfants-Malades, Paris, France;</nlm:aff></affiliation></author><author><name sortKey="Cook, Matthew C" sort="Cook, Matthew C" uniqKey="Cook M" first="Matthew C." last="Cook">Matthew C. Cook</name><affiliation><nlm:aff wicri:cut=", and" id="aff18">Australian National University Medical School</nlm:aff></affiliation><affiliation><nlm:aff id="aff19">John Curtin School of Medical Research, Australian National University, ACT, Canberra, Australia;</nlm:aff></affiliation><affiliation><nlm:aff wicri:cut="; and" id="aff20">Department of Immunology, The Canberra Hospital, Canberra, ACT, Australia</nlm:aff></affiliation></author><author><name sortKey="Casanova, Jean Laurent" sort="Casanova, Jean Laurent" uniqKey="Casanova J" first="Jean-Laurent" last="Casanova">Jean-Laurent Casanova</name><affiliation><nlm:aff id="aff4">Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U980, Necker Medical School, University Paris Descartes, Paris, France;</nlm:aff></affiliation><affiliation><nlm:aff id="aff6">Université Paris Descartes, Institut Imagine, Paris, France;</nlm:aff></affiliation><affiliation><nlm:aff id="aff7">Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY;</nlm:aff></affiliation></author><author><name sortKey="Uzel, Gulbu" sort="Uzel, Gulbu" uniqKey="Uzel G" first="Gulbu" last="Uzel">Gulbu Uzel</name><affiliation><nlm:aff id="aff21">Immunopathogenesis Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD</nlm:aff></affiliation></author><author><name sortKey="Tangye, Stuart G" sort="Tangye, Stuart G" uniqKey="Tangye S" first="Stuart G." last="Tangye">Stuart G. Tangye</name><affiliation><nlm:aff id="aff1">Immunology Research Program, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia;</nlm:aff></affiliation><affiliation><nlm:aff id="aff2">St Vincent’s Clinical School, University of New South Wales, Australia;</nlm:aff></affiliation></author></analytic><series><title level="j">Blood</title><idno type="ISSN">0006-4971</idno><idno type="eISSN">1528-0020</idno><imprint><date when="2013">2013</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><title>Key Points</title><p><list list-type="bullet"><list-item><p>IL21-mediated induction of CD25 expression on naïve human B cells requires STAT3.</p></list-item><list-item><p>A lack of response to IL-2 may amplify humoral immunodeficiency in patients with <italic>STAT3</italic>, <italic>IL2RG</italic>, or <italic>IL21R</italic> mutations due to unresponsiveness to IL21.</p></list-item></list></p></div></front></TEI><pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Blood</journal-id><journal-id journal-id-type="iso-abbrev">Blood</journal-id><journal-id journal-id-type="hwp">bloodjournal</journal-id><journal-id journal-id-type="pmc">blood</journal-id><journal-id journal-id-type="publisher-id">Blood</journal-id><journal-title-group><journal-title>Blood</journal-title></journal-title-group><issn pub-type="ppub">0006-4971</issn><issn pub-type="epub">1528-0020</issn><publisher><publisher-name>American Society of Hematology</publisher-name><publisher-loc>Washington, DC</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">24159173</article-id><article-id pub-id-type="pmc">3854113</article-id><article-id pub-id-type="publisher-id">2013/506865</article-id><article-id pub-id-type="doi">10.1182/blood-2013-06-506865</article-id><article-categories><subj-group subj-group-type="hwp-journal-coll"><subject>12</subject></subj-group><subj-group subj-group-type="heading"><subject>Immunobiology</subject></subj-group></article-categories><title-group><article-title>IL-21 signalling via STAT3 primes human naïve B cells to respond to IL-2 to enhance their differentiation into plasmablasts</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Berglund</surname><given-names>Lucinda J.</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="aff" rid="aff2">2</xref><xref ref-type="aff" rid="aff3">3</xref></contrib><contrib contrib-type="author"><name><surname>Avery</surname><given-names>Danielle T.</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Ma</surname><given-names>Cindy S.</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="aff" rid="aff2">2</xref></contrib><contrib contrib-type="author"><name><surname>Moens</surname><given-names>Leen</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Deenick</surname><given-names>Elissa K.</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="aff" rid="aff2">2</xref></contrib><contrib contrib-type="author"><name><surname>Bustamante</surname><given-names>Jacinta</given-names></name><xref ref-type="aff" rid="aff4">4</xref><xref ref-type="aff" rid="aff5">5</xref><xref ref-type="aff" rid="aff6">6</xref></contrib><contrib contrib-type="author"><name><surname>Boisson-Dupuis</surname><given-names>Stephanie</given-names></name><xref ref-type="aff" rid="aff4">4</xref><xref ref-type="aff" rid="aff7">7</xref></contrib><contrib contrib-type="author"><name><surname>Wong</surname><given-names>Melanie</given-names></name><xref ref-type="aff" rid="aff8">8</xref></contrib><contrib contrib-type="author"><name><surname>Adelstein</surname><given-names>Stephen</given-names></name><xref ref-type="aff" rid="aff9">9</xref></contrib><contrib contrib-type="author"><name><surname>Arkwright</surname><given-names>Peter D.</given-names></name><xref ref-type="aff" rid="aff10">10</xref></contrib><contrib contrib-type="author"><name><surname>Bacchetta</surname><given-names>Rosa</given-names></name><xref ref-type="aff" rid="aff11">11</xref></contrib><contrib contrib-type="author"><name><surname>Bezrodnik</surname><given-names>Liliana</given-names></name><xref ref-type="aff" rid="aff12">12</xref></contrib><contrib contrib-type="author"><name><surname>Dadi</surname><given-names>Harjit</given-names></name><xref ref-type="aff" rid="aff13">13</xref></contrib><contrib contrib-type="author"><name><surname>Roifman</surname><given-names>Chaim M.</given-names></name><xref ref-type="aff" rid="aff13">13</xref></contrib><contrib contrib-type="author"><name><surname>Fulcher</surname><given-names>David A.</given-names></name><xref ref-type="aff" rid="aff3">3</xref></contrib><contrib contrib-type="author"><name><surname>Ziegler</surname><given-names>John B.</given-names></name><xref ref-type="aff" rid="aff14">14</xref></contrib><contrib contrib-type="author"><name><surname>Smart</surname><given-names>Joanne M.</given-names></name><xref ref-type="aff" rid="aff15">15</xref></contrib><contrib contrib-type="author"><name><surname>Kobayashi</surname><given-names>Masao</given-names></name><xref ref-type="aff" rid="aff16">16</xref></contrib><contrib contrib-type="author"><name><surname>Picard</surname><given-names>Capucine</given-names></name><xref ref-type="aff" rid="aff4">4</xref><xref ref-type="aff" rid="aff5">5</xref><xref ref-type="aff" rid="aff6">6</xref></contrib><contrib contrib-type="author"><name><surname>Durandy</surname><given-names>Anne</given-names></name><xref ref-type="aff" rid="aff5">5</xref><xref ref-type="aff" rid="aff6">6</xref><xref ref-type="aff" rid="aff17">17</xref></contrib><contrib contrib-type="author"><name><surname>Cook</surname><given-names>Matthew C.</given-names></name><xref ref-type="aff" rid="aff18">18</xref><xref ref-type="aff" rid="aff19">19</xref><xref ref-type="aff" rid="aff20">20</xref></contrib><contrib contrib-type="author"><name><surname>Casanova</surname><given-names>Jean-Laurent</given-names></name><xref ref-type="aff" rid="aff4">4</xref><xref ref-type="aff" rid="aff6">6</xref><xref ref-type="aff" rid="aff7">7</xref></contrib><contrib contrib-type="author"><name><surname>Uzel</surname><given-names>Gulbu</given-names></name><xref ref-type="aff" rid="aff21">21</xref></contrib><contrib contrib-type="author" corresp="yes"><name><surname>Tangye</surname><given-names>Stuart G.</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="aff" rid="aff2">2</xref></contrib><aff id="aff1"><label>1</label>Immunology Research Program, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia;</aff><aff id="aff2"><label>2</label>St Vincent’s Clinical School, University of New South Wales, Australia;</aff><aff id="aff3"><label>3</label>Department of Immunology, Institute of Clinical Pathology and Medical Research, Westmead Hospital, Westmead, NSW, Australia;</aff><aff id="aff4"><label>4</label>Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U980, Necker Medical School, University Paris Descartes, Paris, France;</aff><aff id="aff5"><label>5</label>Study Center for Primary Immunodeficiencies, AP-HP, Necker Hospital, Paris, France;</aff><aff id="aff6"><label>6</label>Université Paris Descartes, Institut Imagine, Paris, France;</aff><aff id="aff7"><label>7</label>Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY;</aff><aff id="aff8"><label>8</label>Department of Immunology, Children’s Hospital at Westmead, Westmead, NSW, Australia;</aff><aff id="aff9"><label>9</label>Clinical Immunology, Royal Prince Alfred Hospital, Sydney, NSW, Australia;</aff><aff id="aff10"><label>10</label>University of Manchester, Royal Manchester Children’s Hospital, Manchester, United Kingdom;</aff><aff id="aff11"><label>11</label>San Raffaele Telethon Institute for Gene Therapy (HSR-TIGET), San Raffaele Scientific Institute, Milan, Italy;</aff><aff id="aff12"><label>12</label>Immunology Unit, Ricardo Gutiérrez Children Hosptial, Ciudad Autónoma de Buenos Aires, Argentina;</aff><aff id="aff13"><label>13</label>Canadian Centre for Primary Immunodeficiency, Hospital for Sick Children and University of Toronto, Toronto, ON, Canada;</aff><aff id="aff14"><label>14</label>Department of Immunology, Sydney Children's Hospital, Randwick, NSW, Australia and School of Women’s and Children’s Health, University of NSW, Randwick, Australia;</aff><aff id="aff15"><label>15</label>Department of Allergy and Immunology, Royal Children’s Hospital Melbourne, Melbourne, VIC, Australia;</aff><aff id="aff16"><label>16</label>Department of Pediatrics, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, Japan;</aff><aff id="aff17"><label>17</label>INSERM, Unité U768, Hôpital Necker Enfants-Malades, Paris, France;</aff><aff id="aff18"><label>18</label>Australian National University Medical School, and</aff><aff id="aff19"><label>19</label>John Curtin School of Medical Research, Australian National University, ACT, Canberra, Australia;</aff><aff id="aff20"><label>20</label>Department of Immunology, The Canberra Hospital, Canberra, ACT, Australia; and</aff><aff id="aff21"><label>21</label>Immunopathogenesis Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD</aff></contrib-group><pub-date pub-type="ppub"><day>5</day><month>12</month><year>2013</year></pub-date><pub-date pub-type="epreprint"><day>24</day><month>10</month><year>2013</year></pub-date><pub-date pub-type="pmc-release"><day>5</day><month>12</month><year>2014</year></pub-date><volume>122</volume><issue>24</issue><fpage>3940</fpage><lpage>3950</lpage><history><date date-type="received"><day>03</day><month>6</month><year>2013</year></date><date date-type="accepted"><day>10</day><month>10</month><year>2013</year></date></history><permissions><copyright-year>2013</copyright-year></permissions><self-uri xlink:title="pdf" xlink:type="simple" xlink:href="3940.pdf"></self-uri><abstract abstract-type="executive-summary"><title>Key Points</title><p><list list-type="bullet"><list-item><p>IL21-mediated induction of CD25 expression on naïve human B cells requires STAT3.</p></list-item><list-item><p>A lack of response to IL-2 may amplify humoral immunodeficiency in patients with <italic>STAT3</italic>, <italic>IL2RG</italic>, or <italic>IL21R</italic> mutations due to unresponsiveness to IL21.</p></list-item></list></p></abstract><abstract><p>B-cell responses are guided by the integration of signals through the B-cell receptor (BCR), CD40, and cytokine receptors. The common γ chain (γc)-binding cytokine interleukin (IL)-21 drives humoral immune responses via STAT3-dependent induction of transcription factors required for plasma cell generation. We investigated additional mechanisms by which IL-21/STAT3 signaling modulates human B-cell responses by studying patients with <italic>STAT3</italic> mutations. IL-21 strongly induced CD25 (IL-2Rα) in normal, but not STAT3-deficient, CD40L-stimulated naïve B cells. Chromatin immunoprecipitation confirmed <italic>IL2RA</italic> as a direct target of STAT3. IL-21–induced CD25 expression was also impaired on B cells from patients with <italic>IL2RG</italic> or <italic>IL21R</italic> mutations, confirming a requirement for intact IL-21R signaling in this process. IL-2 increased plasmablast generation and immunoglobulin secretion from normal, but not CD25-deficient, naïve B cells stimulated with CD40L/IL-21. IL-2 and IL-21 were produced by T follicular helper cells, and neutralizing both cytokines abolished the B-cell helper capacity of these cells. Our results demonstrate that IL-21, via STAT3, sensitizes B cells to the stimulatory effects of IL-2. Thus, IL-2 may play an adjunctive role in IL-21–induced B-cell differentiation. Lack of this secondary effect of IL-21 may amplify the humoral immunodeficiency in patients with mutations in <italic>STAT3</italic>, <italic>IL2RG</italic>, or <italic>IL21R</italic> due to impaired responsiveness to IL-21.</p></abstract><counts><page-count count="11"></page-count></counts></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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