{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T13:11:33Z","timestamp":1789823493330,"version":"4.0.1"},"reference-count":35,"publisher":"Rockefeller University Press","issue":"10","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2011,9,26]]},"abstract":"<jats:p>Patients with the immunodeficiency Wiskott-Aldrich syndrome (WAS) frequently develop systemic autoimmunity. Here, we demonstrate that mutation of the WAS gene results in B cells that are hyperresponsive to B cell receptor and Toll-like receptor (TLR) signals in vitro, thereby promoting a B cell\u2013intrinsic break in tolerance. Whereas this defect leads to autoantibody production in WAS protein\u2013deficient (WASp\u2212\/\u2212) mice without overt disease, chimeric mice in which only the B cell lineage lacks WASp exhibit severe autoimmunity characterized by spontaneous germinal center formation, class-switched autoantibodies, renal histopathology, and early mortality. Both T cell help and B cell\u2013intrinsic TLR engagement play important roles in promoting disease in this model, as depletion with anti-CD4 antibodies or generation of chimeric mice with B cells deficient in both WASp and MyD88 prevented development of autoimmune disease. These data highlight the potentially harmful role for cell-intrinsic loss of B cell tolerance in the setting of normal T cell function, and may explain why WAS patients with mixed chimerism after stem cell transplantation often develop severe humoral autoimmunity.<\/jats:p>","DOI":"10.1084\/jem.20110200","type":"journal-article","created":{"date-parts":[[2011,8,29]],"date-time":"2011-08-29T20:55:59Z","timestamp":1314651359000},"page":"2033-2042","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":153,"title":["WASp-deficient B cells play a critical, cell-intrinsic role in triggering autoimmunity"],"prefix":"10.1084","volume":"208","author":[{"given":"Shirly","family":"Becker-Herman","sequence":"first","affiliation":[{"name":"Department of Pediatrics 1 , 2 , 3 , and 4"},{"name":"Department of Immunology 1 , 2 , 3 , and 4"},{"name":"Department of Pathology 1 , 2 , 3 , and 4"},{"name":"Department of Comparative Medicine, 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