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B\u2010cell\u2010intrinsic deletion of the affected gene WAS protein (WASp) markedly reduces splenic MZ B cells, without impacting the rate of MZ B\u2010cell development, suggesting that abnormal B\u2010cell retention within the MZ accounts for MZ defects in WAS. Since WASp regulates integrin\u2010dependent actin cytoskeletal rearrangement, we previously hypothesized that defective B\u2010cell integrin function promotes MZ depletion. In contrast, we now report that B\u2010cell\u2010intrinsic deletion of the TLR signaling adaptor MyD88 is sufficient to restore the MZ in WAS. We further identify TLR7, an endosomal single\u2010stranded RNA (ssRNA) receptor, as the MyD88\u2010dependent receptor responsible for WAS MZ depletion. These findings implicate spontaneous activation of MZ B cells by ssRNA\u2010containing self\u2010ligands (likely derived from circulating apoptotic material) as the mechanism underlying MZ depletion in WAS. Together, these data suggest a previously unappreciated role for B\u2010cell intrinsic TLR signals in MZ homeostasis, of relevance to both pathogen responses and to the development of systemic autoimmunity.<\/jats:p>","DOI":"10.1002\/eji.201545644","type":"journal-article","created":{"date-parts":[[2015,8,8]],"date-time":"2015-08-08T08:46:49Z","timestamp":1439023609000},"page":"2773-2779","source":"Crossref","is-referenced-by-count":19,"title":["B\u2010cell intrinsic TLR7 signals promote depletion of the marginal zone in a murine model of Wiskott\u2013Aldrich syndrome"],"prefix":"10.1002","volume":"45","author":[{"given":"Nikita S.","family":"Kolhatkar","sequence":"first","affiliation":[{"name":"Seattle Children's Research Institute  Seattle WA USA"},{"name":"Department of Immunology University of Washington School of Medicine  Seattle WA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicole 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