{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T01:21:42Z","timestamp":1789435302314,"version":"build-2803163510"},"reference-count":49,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2010,4,14]],"date-time":"2010-04-14T00:00:00Z","timestamp":1271203200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[2010,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Accumulation of plasma cells and autoantibodies against nuclear antigens characterize both human and murine lupus. Understanding how these processes are controlled may reveal novel therapeutic targets for this disease. Mice deficient in Lyn, a negative regulator of B and myeloid cell activity, develop lupus\u2010like autoimmune disease. Here, we show that <jats:italic>lyn<jats:sup>\u2212<\/jats:sup><jats:sup>\/<\/jats:sup><jats:sup>\u2212<\/jats:sup><\/jats:italic> mice exhibit increased splenic plasmablasts and plasma cells and produce IgM against a wide range of self\u2010antigens. Both events require Btk, a target of Lyn\u2010dependent inhibitory pathways. A Btk\u2010dependent increase in the expression of the plasma cell survival factor IL\u20106 by <jats:italic>lyn<jats:sup>\u2212<\/jats:sup><jats:sup>\/<\/jats:sup><jats:sup>\u2212<\/jats:sup><\/jats:italic> splenic myeloid cells was also observed. Surprisingly, IL\u20106 was not required for plasma cell accumulation or polyclonal IgM autoreactivity in <jats:italic>lyn<jats:sup>\u2212\/\u2212<\/jats:sup><\/jats:italic> mice. IL\u20106 was, however, necessary for the production of IgG autoantibodies, which we show are focused towards a limited set of nucleic acid\u2010containing and glomerular autoantigens in <jats:italic>lyn<jats:sup>\u2212<\/jats:sup><jats:sup>\/<\/jats:sup><jats:sup>\u2212<\/jats:sup><\/jats:italic> mice. A similar uncoupling of plasma cell accumulation from IgG autoantibodies was seen in <jats:italic>lyn<jats:sup>+\/\u2212<\/jats:sup><\/jats:italic> mice. Plasma cell accumulation and polyclonal IgM autoreactivity are therefore controlled separately from, and are insufficient for, the production of IgG against lupus\u2010associated autoantigens. Regulators of either of these two checkpoints may be attractive therapeutic targets for lupus.<\/jats:p>","DOI":"10.1002\/eji.200940043","type":"journal-article","created":{"date-parts":[[2010,4,14]],"date-time":"2010-04-14T23:11:45Z","timestamp":1271286705000},"page":"1897-1905","source":"Crossref","is-referenced-by-count":27,"title":["Separate checkpoints regulate splenic plasma cell accumulation and IgG autoantibody production in Lyn\u2010deficient mice"],"prefix":"10.1002","volume":"40","author":[{"given":"Toni","family":"Gutierrez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristina E.","family":"Halcomb","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alanna 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