{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:06:14Z","timestamp":1791331574097,"version":"4.3.1"},"reference-count":37,"publisher":"National Academy of Sciences","issue":"38","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2012,9,18]]},"abstract":"<jats:p>\n                    Mutations in TNFRSF13B, better known as transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI), contribute to common variable immunodeficiency and autoimmunity in humans. How TACI regulates these two opposing conditions is unclear, however. TACI binds the cytokines BAFF and APRIL, and previous studies using gene KO mice indicated that loss of TACI affected only T-cell\u2013independent antibody responses. Here we demonstrate that\n                    <jats:italic>Taci<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    mice have expanded populations of T follicular helper (T\n                    <jats:sub>fh<\/jats:sub>\n                    ) and germinal center (GC) B cells in their spleens when immunized with T-cell\u2013dependent antigen. The increased numbers of T\n                    <jats:sub>fh<\/jats:sub>\n                    and GC B cells in\n                    <jats:italic>Taci<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    mice are largely a result of up-regulation of inducible costimulator (ICOS) ligand on TACI-deficient B cells, given that ablation of one copy of the\n                    <jats:italic>Icosl<\/jats:italic>\n                    allele restores normal levels of T\n                    <jats:sub>fh<\/jats:sub>\n                    and GC B cells in\n                    <jats:italic>Taci<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    mice. Interestingly, despite the presence of increased T\n                    <jats:sub>fh<\/jats:sub>\n                    and antigen-specific B cells, immunized\n                    <jats:italic>Taci<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    mice demonstrate defective antigen-specific antibody responses resulting from significantly reduced numbers of antibody-secreting cells (ASCs). This effect is attributed to the failure to down-regulate the proapoptotic molecule BIM in\n                    <jats:italic>Taci<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    plasma cells. Ablation of BIM could rescue ASC formation in\n                    <jats:italic>Taci<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    mice, suggesting that TACI is more important for the survival of plasma cells than for the differentiation of these cells. Thus, our data reveal dual roles for TACI in B-cell terminal differentiation. On one hand, TACI modulates ICOS ligand expression and thereby limits the size of T\n                    <jats:sub>fh<\/jats:sub>\n                    and GC B-cell compartments and prevents autoimmunity. On the other hand, it regulates the survival of ASCs and plays an important role in humoral immunity.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1200386109","type":"journal-article","created":{"date-parts":[[2012,9,4]],"date-time":"2012-09-04T20:17:32Z","timestamp":1346789852000},"page":"15401-15406","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":99,"title":["Deficiency in TNFRSF13B (TACI) expands T-follicular helper and germinal center B cells via increased ICOS-ligand expression but impairs plasma cell survival"],"prefix":"10.1073","volume":"109","author":[{"given":"Xijun","family":"Ou","sequence":"first","affiliation":[{"name":"Immunology Group, Bioprocessing Technology Institute, Agency for Science, Technology and Research, Singapore;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengli","family":"Xu","sequence":"additional","affiliation":[{"name":"Immunology Group, Bioprocessing Technology Institute, Agency for Science, Technology and Research, Singapore;"},{"name":"Departments of bPhysiology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kong-Peng","family":"Lam","sequence":"additional","affiliation":[{"name":"Immunology Group, Bioprocessing Technology Institute, Agency for Science, Technology and Research, Singapore;"},{"name":"Departments of bPhysiology,"},{"name":"Microbiology, and"},{"name":"Pediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117599"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2012,9,4]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cytogfr.2008.04.006"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.173.4.2331"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20031330"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1600"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1601"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1006\/clim.1999.4725"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(01)00130-3"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/89790"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri2217"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-031210-101400"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2008.05.009"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.173.2.807"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.179.11.7276"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20032000"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-11-189720"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2010.08.017"},{"key":"e_1_3_3_17_2","doi-asserted-by":"crossref","first-page":"2698","DOI":"10.4049\/jimmunol.129.6.2698","article-title":"Surface phenotype of Peyer\u2019s patch germinal center cells: Implications for the role of germinal centers in B cell differentiation","volume":"129","author":"Butcher EC","year":"1982","unstructured":"EC Butcher, et al., Surface phenotype of Peyer\u2019s patch germinal center cells: Implications for the role of germinal centers in B cell differentiation. 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