{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T17:47:03Z","timestamp":1791136023767,"version":"4.1.0"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2006,2,1]],"date-time":"2006-02-01T00:00:00Z","timestamp":1138752000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2006,2,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Smad2 is a member of the intracellular mediators that transduce signals from TGF-\u03b2 receptors and activin receptors. Targeted inactivation of Smad2 in mice leads to early lethality before gastrulation. It was shown previously that TGF-\u03b2RII deficiency in vivo leads to defects in B cell homeostasis, Ag responsiveness, and IgA class switch recombination of B cells. To investigate the importance of Smad2-mediated signaling in B lymphocytes, we generated a B cell-specific inactivation of Smad2 in mice (bSmad2\u2212\/\u2212). bSmad2\u2212\/\u2212 mice had normal B cell numbers in the spleen but showed a reduced population of marginal zone B cells. In contrast, B cells in Peyer\u2019s patches and peritoneal B-1a cells of bSmad2\u2212\/\u2212 mice were increased in numbers. bSmad2\u2212\/\u2212 mice showed a reduced number of surface-IgA+ B cells and of IgA-secreting cells in Peyer\u2019s patches, decreased levels of IgA in serum, and, after immunization with a T cell-dependent Ag, a reduced IgA response. Class switch recombination to IgA was impaired in Smad2-deficient B cells, when stimulated in vitro with LPS in the presence of TGF-\u03b2. The growth-inhibitory effects of TGF-\u03b2 in LPS-stimulated B cells were not affected in Smad2-deficient B cells. In summary, our data indicate a crucial role of Smad2 in mediating signals for the TGF-\u03b2-directed class switch to IgA and the induction of IgA responses in vivo. Other B cell functions like growth-inhibitory signaling, which are known to be regulated by signals via the TGF-\u03b2R, are not affected in Smad2-deficient B cells.<\/jats:p>","DOI":"10.4049\/jimmunol.176.4.2389","type":"journal-article","created":{"date-parts":[[2014,4,20]],"date-time":"2014-04-20T20:31:56Z","timestamp":1398025916000},"page":"2389-2396","source":"Crossref","is-referenced-by-count":42,"title":["B Cell-Specific Deficiency for Smad2 In Vivo Leads to Defects in TGF-\u03b2-Directed IgA Switching and Changes in B Cell Fate"],"prefix":"10.1093","volume":"176","author":[{"given":"Jo\u0308rg","family":"Klein","sequence":"first","affiliation":[{"name":"Institute for Virology and Immunobiology, University of Wu\u0308rzburg , Wu\u0308rzburg ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjun","family":"Ju","sequence":"additional","affiliation":[{"name":"Department of Medicine, Mount Sinai School of Medicine , New York, NY 10029"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jo\u0308rg","family":"Heyer","sequence":"additional","affiliation":[{"name":"Department of Medicine, Mount Sinai School of Medicine , New York, NY 10029"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Britta","family":"Wittek","sequence":"additional","affiliation":[{"name":"Department of Physiological Chemistry II, Biocenter, University of Wu\u0308rzburg , Wu\u0308rzburg ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Torsten","family":"Haneke","sequence":"additional","affiliation":[{"name":"Department of Physiological Chemistry I, Biocenter, University of Wu\u0308rzburg , Wu\u0308rzburg ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petra","family":"Knaus","sequence":"additional","affiliation":[{"name":"Department of Physiological Chemistry II, Biocenter, University of Wu\u0308rzburg , Wu\u0308rzburg ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raju","family":"Kucherlapati","sequence":"additional","affiliation":[{"name":"Brigham and Women\u2019s Hospital, Harvard Medical School , Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erwin P","family":"Bo\u0308ttinger","sequence":"additional","affiliation":[{"name":"Department of Medicine, Mount Sinai School of Medicine , New York, NY 10029"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Nitschke","sequence":"additional","affiliation":[{"name":"Institute for Virology and Immunobiology, University of Wu\u0308rzburg , Wu\u0308rzburg ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Burkhard","family":"Kneitz","sequence":"additional","affiliation":[{"name":"Department of Physiological Chemistry I, Biocenter, University of Wu\u0308rzburg , Wu\u0308rzburg ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2006,2,15]]},"reference":[{"key":"2026020211391910800_R1","first-page":"577","volume-title":"Nature","year":"2003"},{"key":"2026020211391910800_R2","first-page":"731","volume-title":"J. 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