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These <jats:styled-content style=\"fixed-case\">CPA<\/jats:styled-content>bs are polyreactive because they bind to <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> and other cellular components, and localize mainly in the nucleus of HeLa cells, albeit with a distinct nuclear labelling profile. Herein, we have examined whether <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content>\u2013histone complexes (<jats:styled-content style=\"fixed-case\">DHC<\/jats:styled-content>) binding to <jats:styled-content style=\"fixed-case\">CPA<\/jats:styled-content>bs, before cell entry, could modify the cell penetration of <jats:styled-content style=\"fixed-case\">CPA<\/jats:styled-content>bs or their nuclear staining properties. By applying confocal microscopy and image analysis, we found that extracellular binding of purified <jats:styled-content style=\"fixed-case\">CPA<\/jats:styled-content>bs to <jats:styled-content style=\"fixed-case\">DHC<\/jats:styled-content> significantly enhanced their subsequent cell\u2010entry, both in terms of percentages of positively labelled cells and fluorescence intensity (internalized <jats:styled-content style=\"fixed-case\">CPA<\/jats:styled-content>b amount), whereas there was a variable effect on their nuclear staining profile. Internalization of <jats:styled-content style=\"fixed-case\">CPA<\/jats:styled-content>bs, either alone or bound to <jats:styled-content style=\"fixed-case\">DHC<\/jats:styled-content>, remained unaltered after the addition of endocytosis\u2010specific inhibitors at 37\u00b0 or assay performance at 4\u00b0, suggesting the involvement of energy\u2010independent mechanisms in the internalization process. These findings assign to <jats:styled-content style=\"fixed-case\">CPA<\/jats:styled-content>bs a more complex pathogenetic role in systemic lupus erythematosus where both <jats:styled-content style=\"fixed-case\">CPA<\/jats:styled-content>bs and nuclear components are abundant.<\/jats:p>","DOI":"10.1111\/imm.12542","type":"journal-article","created":{"date-parts":[[2015,10,8]],"date-time":"2015-10-08T17:33:41Z","timestamp":1444325621000},"page":"73-81","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["<scp>DNA<\/scp>\u2013histone complexes as ligands amplify cell penetration and nuclear targeting of anti\u2010<scp>DNA<\/scp> antibodies via energy\u2010independent mechanisms"],"prefix":"10.1111","volume":"147","author":[{"given":"Markella","family":"Zannikou","sequence":"first","affiliation":[{"name":"Immunology Laboratory Immunology Department Hellenic Pasteur Institute Athens 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