{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T06:32:25Z","timestamp":1790836345288,"version":"4.1.0"},"reference-count":25,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2015,2,1]],"date-time":"2015-02-01T00:00:00Z","timestamp":1422748800000},"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":[[2015,2,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>In mice that fail to express the phagolysosomal endonuclease DNase II and the type I IFN receptor, excessive accrual of undegraded DNA results in a STING-dependent, TLR-independent inflammatory arthritis. These double-knockout (DKO) mice develop additional indications of systemic autoimmunity, including anti-nuclear autoantibodies and splenomegaly, that are not found in Unc93b13d\/3d DKO mice and, therefore, are TLR dependent. The DKO autoantibodies predominantly detect RNA-associated autoantigens, which are commonly targeted in TLR7-dominated systemic erythematosus lupus\u2013prone mice. To determine whether an inability of TLR9 to detect endogenous DNA could explain the absence of dsDNA-reactive autoantibodies in DKO mice, we used a novel class of bifunctional autoantibodies, IgM\/DNA dual variable domain Ig molecules, to activate B cells through a BCR\/TLR9-dependent mechanism. DKO B cells could not respond to the IgM\/DNA dual variable domain Ig molecule, despite a normal response to both anti-IgM and CpG ODN 1826. Thus, DKO B cells only respond to RNA-associated ligands because DNase II\u2013mediated degradation of self-DNA is required for TLR9 activation.<\/jats:p>","DOI":"10.4049\/jimmunol.1402893","type":"journal-article","created":{"date-parts":[[2015,1,20]],"date-time":"2015-01-20T05:11:30Z","timestamp":1421730690000},"page":"1403-1407","source":"Crossref","is-referenced-by-count":54,"title":["Cutting Edge: DNase II Deficiency Prevents Activation of Autoreactive B Cells by Double-Stranded DNA Endogenous Ligands"],"prefix":"10.1093","volume":"194","author":[{"given":"Sudesh","family":"Pawaria","sequence":"first","affiliation":[{"name":"Department of Medicine, University of Massachusetts School of Medicine , Worcester, MA 01605"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krishna","family":"Moody","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Massachusetts School of Medicine , Worcester, MA 01605"},{"name":"Department of Microbiology, Boston University School of Medicine , Boston, MA 02118"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Busto","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Massachusetts School of Medicine , Worcester, MA 01605"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerstin","family":"N\u00fcndel","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Massachusetts School of Medicine , Worcester, MA 01605"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chee-Ho","family":"Choi","sequence":"additional","affiliation":[{"name":"Global Biologics, AbbVie BioResearch Center , Worcester, MA 01605"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tariq","family":"Ghayur","sequence":"additional","affiliation":[{"name":"Global Biologics, AbbVie BioResearch Center , Worcester, MA 01605"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann","family":"Marshak-Rothstein","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Massachusetts School of Medicine , Worcester, MA 01605"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2015,2,15]]},"reference":[{"key":"2025030705065528000_r1","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1038\/ni1146","article-title":"Lethal anemia caused by interferon-beta produced in mouse embryos carrying undigested DNA","volume":"6","author":"Yoshida","year":"2005","journal-title":"Nat. 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