{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T15:33:29Z","timestamp":1781105609152,"version":"3.54.1"},"reference-count":40,"publisher":"National Academy of Sciences","issue":"13","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2005,3,29]]},"abstract":"<jats:p>\n                    More than half of patients with X-linked lympho-proliferative disease, which is caused by a defect in the intracellular adapter protein SH2D1A, suffer from an extreme susceptibility to Epstein-Barr virus. One-third of these patients, however, develop dysgammaglobulenemia without an episode of severe mononucleosis. Here we show that in\n                    <jats:italic>SH2D1A<\/jats:italic>\n                    <jats:sup>\n                      -\n                      <jats:italic>\/<\/jats:italic>\n                      -\n                    <\/jats:sup>\n                    mice, both primary and secondary responses of all Ig subclasses are severely impaired in response to specific antigens. Because germinal centers were absent in\n                    <jats:italic>SH2D1A<\/jats:italic>\n                    <jats:sup>\n                      -\n                      <jats:italic>\/<\/jats:italic>\n                      -\n                    <\/jats:sup>\n                    mice upon primary immunization, and because SH2D1A was detectable in\n                    <jats:italic>wt<\/jats:italic>\n                    germinal center B cells, we examined whether\n                    <jats:italic>SH2D1A<\/jats:italic>\n                    <jats:sup>\n                      -\n                      <jats:italic>\/<\/jats:italic>\n                      -\n                    <\/jats:sup>\n                    B cell functions were impaired. Using the adoptive cotransfer of B lymphocytes from hapten-primed\n                    <jats:italic>SH2D1A<\/jats:italic>\n                    <jats:sup>\n                      -\n                      <jats:italic>\/<\/jats:italic>\n                      -\n                    <\/jats:sup>\n                    mice with CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells from primed\n                    <jats:italic>wt<\/jats:italic>\n                    mice into irradiated\n                    <jats:italic>wt<\/jats:italic>\n                    mice provided evidence that signal transduction events controlled by SH2D1A are essential for B cell activities resulting in antigen specific IgG production. Defects in na\u00efve\n                    <jats:italic>SH2D1A<\/jats:italic>\n                    <jats:sup>\n                      -\n                      <jats:italic>\/<\/jats:italic>\n                      -\n                    <\/jats:sup>\n                    B cells became evident upon cotransfer with non-primed\n                    <jats:italic>wt<\/jats:italic>\n                    CD4\n                    <jats:sup>+<\/jats:sup>\n                    cells into\n                    <jats:italic>Rag2<\/jats:italic>\n                    <jats:sup>\n                      -\n                      <jats:italic>\/<\/jats:italic>\n                      -\n                    <\/jats:sup>\n                    recipients. Thus, both defective T and B cells exist in the absence of SH2D1A, which may explain the progressive dysgammaglobulinemia in a subset of X-linked lympho-proliferative disease patients without involvement of Epstein-Barr virus.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0408681102","type":"journal-article","created":{"date-parts":[[2005,3,17]],"date-time":"2005-03-17T23:53:22Z","timestamp":1111103602000},"page":"4819-4823","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":52,"title":["Defective B cell responses in the absence of SH2D1A"],"prefix":"10.1073","volume":"102","author":[{"given":"Massimo","family":"Morra","sequence":"first","affiliation":[{"name":"Division of Immunology, Beth Israel Deaconess Medical Center, Harvard Medical School, and CBR Institute for Biomedical Research and Department of Pathology, Harvard University, Boston, MA 02215; Edward Jenner Institute for Vaccine Research, Compton, Newbury, Berkshire RG20 7NN, United Kingdom; Department of Pathology, Tufts University School of Medicine, 150 Harrison Avenue, Boston, MA 02111; Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, Bethesda, MD 20892;..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert A.","family":"Barrington","sequence":"additional","affiliation":[{"name":"Division of Immunology, Beth Israel Deaconess Medical Center, Harvard Medical School, and CBR Institute for Biomedical Research and Department of Pathology, Harvard University, Boston, MA 02215; Edward Jenner Institute for Vaccine Research, Compton, Newbury, Berkshire RG20 7NN, United Kingdom; Department of Pathology, Tufts University School of Medicine, 150 Harrison Avenue, Boston, MA 02111; Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, Bethesda, MD 20892;..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana C.","family":"Abadia-Molina","sequence":"additional","affiliation":[{"name":"Division of Immunology, Beth Israel Deaconess Medical Center, Harvard Medical School, and CBR Institute for Biomedical Research and Department of Pathology, Harvard University, Boston, MA 02215; Edward Jenner Institute for Vaccine Research, Compton, Newbury, Berkshire RG20 7NN, United Kingdom; Department of Pathology, Tufts University School of Medicine, 150 Harrison Avenue, Boston, MA 02111; Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, Bethesda, MD 20892;..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susumo","family":"Okamoto","sequence":"additional","affiliation":[{"name":"Division of Immunology, Beth Israel Deaconess Medical Center, Harvard Medical School, and CBR Institute for Biomedical Research and Department of Pathology, Harvard University, Boston, MA 02215; Edward Jenner Institute for Vaccine Research, Compton, Newbury, Berkshire RG20 7NN, United Kingdom; Department of Pathology, Tufts University School of Medicine, 150 Harrison Avenue, Boston, MA 02111; Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, Bethesda, MD 20892;..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aimee","family":"Julien","sequence":"additional","affiliation":[{"name":"Division of Immunology, Beth Israel Deaconess Medical Center, Harvard Medical School, and CBR Institute for Biomedical Research and Department of Pathology, Harvard University, Boston, MA 02215; Edward Jenner Institute for Vaccine Research, Compton, Newbury, Berkshire RG20 7NN, United Kingdom; Department of Pathology, Tufts University School of Medicine, 150 Harrison Avenue, Boston, MA 02111; Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, Bethesda, MD 20892;..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Gullo","sequence":"additional","affiliation":[{"name":"Division of Immunology, Beth Israel Deaconess Medical Center, Harvard Medical School, and CBR Institute for Biomedical Research and Department of Pathology, Harvard University, Boston, MA 02215; Edward Jenner Institute for Vaccine Research, Compton, Newbury, Berkshire RG20 7NN, United Kingdom; Department of Pathology, Tufts University School of Medicine, 150 Harrison Avenue, Boston, MA 02111; Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, Bethesda, MD 20892;..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anuj","family":"Kalsy","sequence":"additional","affiliation":[{"name":"Division of Immunology, Beth Israel Deaconess Medical Center, Harvard Medical School, and CBR Institute for Biomedical Research and Department of Pathology, Harvard University, Boston, MA 02215; Edward Jenner Institute for Vaccine Research, Compton, Newbury, Berkshire RG20 7NN, United Kingdom; Department of Pathology, Tufts University School of Medicine, 150 Harrison Avenue, Boston, MA 02111; Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, Bethesda, MD 20892;..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew J.","family":"Edwards","sequence":"additional","affiliation":[{"name":"Division of Immunology, Beth Israel Deaconess Medical Center, Harvard Medical School, and CBR Institute for Biomedical Research and Department of Pathology, Harvard University, Boston, MA 02215; Edward Jenner Institute for Vaccine Research, Compton, Newbury, Berkshire RG20 7NN, United Kingdom; Department of Pathology, Tufts University School of Medicine, 150 Harrison Avenue, Boston, MA 02111; Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, Bethesda, MD 20892;..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Immunology, Beth Israel Deaconess Medical Center, Harvard Medical School, and CBR Institute for Biomedical Research and Department of Pathology, Harvard University, Boston, MA 02215; Edward Jenner Institute for Vaccine Research, Compton, Newbury, Berkshire RG20 7NN, United Kingdom; Department of Pathology, Tufts University School of Medicine, 150 Harrison Avenue, Boston, MA 02111; Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, Bethesda, MD 20892;..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosanne","family":"Spolski","sequence":"additional","affiliation":[{"name":"Division of Immunology, Beth Israel Deaconess Medical Center, Harvard Medical School, and CBR Institute for Biomedical Research and Department of Pathology, Harvard University, Boston, MA 02215; Edward Jenner Institute for Vaccine Research, Compton, Newbury, Berkshire RG20 7NN, United Kingdom; Department of Pathology, Tufts University School of Medicine, 150 Harrison Avenue, Boston, MA 02111; Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, Bethesda, MD 20892;..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Warren J.","family":"Leonard","sequence":"additional","affiliation":[{"name":"Division of Immunology, Beth Israel Deaconess Medical Center, Harvard Medical School, and CBR Institute for Biomedical Research and Department of Pathology, Harvard University, Boston, MA 02215; Edward Jenner Institute for Vaccine Research, Compton, Newbury, Berkshire RG20 7NN, United Kingdom; Department of Pathology, Tufts University School of Medicine, 150 Harrison Avenue, Boston, MA 02111; Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, Bethesda, MD 20892;..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brigitte T.","family":"Huber","sequence":"additional","affiliation":[{"name":"Division of Immunology, Beth Israel Deaconess Medical Center, Harvard Medical School, and CBR Institute for Biomedical Research and Department of Pathology, Harvard University, Boston, MA 02215; Edward Jenner Institute for Vaccine Research, Compton, Newbury, Berkshire RG20 7NN, United Kingdom; Department of Pathology, Tufts University School of Medicine, 150 Harrison Avenue, Boston, MA 02111; Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, Bethesda, MD 20892;..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Persephone","family":"Borrow","sequence":"additional","affiliation":[{"name":"Division of Immunology, Beth Israel Deaconess Medical Center, Harvard Medical School, and CBR Institute for Biomedical Research and Department of Pathology, Harvard University, Boston, MA 02215; Edward Jenner Institute for Vaccine Research, Compton, Newbury, Berkshire RG20 7NN, United Kingdom; Department of Pathology, Tufts University School of Medicine, 150 Harrison Avenue, Boston, MA 02111; Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, Bethesda, MD 20892;..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine A.","family":"Biron","sequence":"additional","affiliation":[{"name":"Division of Immunology, Beth Israel Deaconess Medical Center, Harvard Medical School, and CBR Institute for Biomedical Research and Department of Pathology, Harvard University, Boston, MA 02215; Edward Jenner Institute for Vaccine Research, Compton, Newbury, Berkshire RG20 7NN, United Kingdom; Department of Pathology, Tufts University School of Medicine, 150 Harrison Avenue, Boston, MA 02111; Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, Bethesda, MD 20892;..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abhay R.","family":"Satoskar","sequence":"additional","affiliation":[{"name":"Division of Immunology, Beth Israel Deaconess Medical Center, Harvard Medical School, and CBR Institute for Biomedical Research and Department of Pathology, Harvard University, Boston, MA 02215; Edward Jenner Institute for Vaccine Research, Compton, Newbury, Berkshire RG20 7NN, United Kingdom; Department of Pathology, Tufts University School of Medicine, 150 Harrison Avenue, Boston, MA 02111; Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, Bethesda, MD 20892;..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael C.","family":"Carroll","sequence":"additional","affiliation":[{"name":"Division of Immunology, Beth Israel Deaconess Medical Center, Harvard Medical School, and CBR Institute for Biomedical Research and Department of Pathology, Harvard University, Boston, MA 02215; Edward Jenner Institute for Vaccine Research, Compton, Newbury, Berkshire RG20 7NN, United Kingdom; Department of Pathology, Tufts University School of Medicine, 150 Harrison Avenue, Boston, MA 02111; Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, Bethesda, MD 20892;..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cox","family":"Terhorst","sequence":"additional","affiliation":[{"name":"Division of Immunology, Beth Israel Deaconess Medical Center, Harvard Medical School, and CBR Institute for Biomedical Research and Department of Pathology, Harvard University, Boston, MA 02215; Edward Jenner Institute for Vaccine Research, Compton, Newbury, Berkshire RG20 7NN, United Kingdom; Department of Pathology, Tufts University School of Medicine, 150 Harrison Avenue, Boston, MA 02111; Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, Bethesda, MD 20892;..."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2005,3,17]]},"reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(75)92004-8"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9343(77)90318-7"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(80)80735-9"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1203\/00006450-199510000-00001"},{"key":"e_1_3_2_5_2","first-page":"325","volume":"1","year":"1989","unstructured":"Sullivan, J. 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