{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T00:36:59Z","timestamp":1784335019151,"version":"3.55.0"},"reference-count":52,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2017,10,3]],"date-time":"2017-10-03T00:00:00Z","timestamp":1506988800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Kreftforeningen (NO)","award":["420156"],"award-info":[{"award-number":["420156"]}]},{"DOI":"10.13039\/501100006133","name":"Anders Jahres Fond til Vitenskapens Fremme","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006133","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Blix Family Foundation"},{"name":"Freia Foundation"},{"name":"Nansen Foundation"},{"name":"UNIFOR FRIMED legacy"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0185708","type":"journal-article","created":{"date-parts":[[2017,10,3]],"date-time":"2017-10-03T17:40:26Z","timestamp":1507052426000},"page":"e0185708","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":6,"title":["TLR9 stimulation of B-cells induces transcription of p53 and prevents spontaneous and irradiation-induced cell death independent of DNA damage responses. Implications for Common variable immunodeficiency"],"prefix":"10.1371","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1688-7262","authenticated-orcid":true,"given":"Kristine Lilleb\u00f8","family":"Holm","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Randi Gussgard","family":"Sylju\u00e5sen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grete","family":"Hasvold","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lene","family":"Als\u00f8e","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hilde","family":"Nilsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristina","family":"Ivanauskiene","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Collas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergey","family":"Shaposhnikov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Collins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Randi Larsen","family":"Indrev\u00e6r","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P\u00e5l","family":"Aukrust","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B\u00f8rre","family":"Fevang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8537-5439","authenticated-orcid":true,"given":"Heidi Kiil","family":"Blomhoff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2017,10,3]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1146\/annurev-med-081313-121208","article-title":"The DNA damage response: implications for tumor responses to radiation and chemotherapy","volume":"66","author":"M Goldstein","year":"2015","journal-title":"Annu Rev Med"},{"issue":"2","key":"ref2","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.molcel.2010.09.019","article-title":"The DNA damage response: making it safe to play with knives","volume":"40","author":"A Ciccia","year":"2010","journal-title":"Mol Cell"},{"issue":"6422","key":"ref3","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1038\/362709a0","article-title":"Instability and decay of the primary structure of DNA","volume":"362","author":"T Lindahl","year":"1993","journal-title":"Nature"},{"issue":"7267","key":"ref4","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1038\/nature08467","article-title":"The DNA-damage response in human biology and disease","volume":"461","author":"SP Jackson","year":"2009","journal-title":"Nature"},{"issue":"12","key":"ref5","doi-asserted-by":"crossref","first-page":"1809","DOI":"10.1002\/cncr.29841","article-title":"Therapeutic radiation and the potential risk of second malignancies","volume":"122","author":"SC Kamran","year":"2016","journal-title":"Cancer"},{"issue":"10","key":"ref6","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.6004\/jnccn.2015.0151","article-title":"Survival in Patients With Severe Lymphopenia Following Treatment With Radiation and Chemotherapy for Newly Diagnosed Solid Tumors","volume":"13","author":"SA Grossman","year":"2015","journal-title":"J Natl Compr Canc Netw"},{"issue":"1","key":"ref7","first-page":"121","article-title":"Radiation sensitivity of human and murine peripheral blood lymphocytes, stem and progenitor cells","volume":"1846","author":"D Heylmann","year":"2014","journal-title":"Biochim Biophys Acta"},{"issue":"1","key":"ref8","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1111\/imm.12629","article-title":"Myeloid cell leukaemia 1 has a vital role in retinoic acid-mediated protection of Toll-like receptor 9-stimulated B cells from spontaneous and DNA damage-induced apoptosis","volume":"149","author":"KL Holm","year":"2016","journal-title":"Immunology"},{"issue":"10","key":"ref9","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1586\/1744666X.2013.836967","article-title":"Common variable immunodeficiency in adults: current diagnostic protocol and laboratory measures","volume":"9","author":"Y Kumar","year":"2013","journal-title":"Expert Rev Clin Immunol"},{"issue":"2","key":"ref10","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1111\/j.1365-2249.1994.tb06073.x","article-title":"Enhanced generation of reactive oxygen species in monocytes from patients with common variable immunodeficiency","volume":"97","author":"P Aukrust","year":"1994","journal-title":"Clin Exp Immunol"},{"issue":"4","key":"ref11","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.1182\/blood.V86.4.1383.bloodjournal8641383","article-title":"Decreased levels of total and reduced glutathione in CD4+ lymphocytes in common variable immunodeficiency are associated with activation of the tumor necrosis factor system: possible immunopathogenic role of oxidative stress","volume":"86","author":"P Aukrust","year":"1995","journal-title":"Blood"},{"issue":"1","key":"ref12","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1111\/cei.12150","article-title":"CD27+ B cells from a subgroup of common variable immunodeficiency patients are less sensitive to apoptosis rescue regardless of interleukin-21 signalling","volume":"174","author":"A Clemente","year":"2013","journal-title":"Clin Exp Immunol"},{"issue":"1","key":"ref13","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1111\/j.1365-2249.1995.tb06630.x","article-title":"B cells from a distinct subset of patients with common variable immunodeficiency (CVID) have increased CD95 (Apo-1\/fas), diminished CD38 expression, and undergo enhanced apoptosis","volume":"102","author":"A Saxon","year":"1995","journal-title":"Clin Exp Immunol"},{"issue":"7","key":"ref14","doi-asserted-by":"crossref","first-page":"1650","DOI":"10.1182\/blood-2011-09-377945","article-title":"Morbidity and mortality in common variable immune deficiency over 4 decades","volume":"119","author":"ES Resnick","year":"2012","journal-title":"Blood"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.molimm.2015.12.016","article-title":"Role of apoptosis in common variable immunodeficiency and selective immunoglobulin A deficiency","volume":"71","author":"R Yazdani","year":"2016","journal-title":"Mol Immunol"},{"issue":"5","key":"ref16","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1016\/j.imbio.2007.10.018","article-title":"Chromosomal radiosensitivity in patients with common variable immunodeficiency","volume":"213","author":"A Aghamohammadi","year":"2008","journal-title":"Immunobiology"},{"issue":"2","key":"ref17","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/j.jaci.2009.05.019","article-title":"Toll-like receptor 7 and 9 defects in common variable immunodeficiency","volume":"124","author":"JE Yu","year":"2009","journal-title":"J Allergy Clin Immunol"},{"issue":"3","key":"ref18","doi-asserted-by":"crossref","first-page":"1978","DOI":"10.4049\/jimmunol.176.3.1978","article-title":"TLR9 activation is defective in common variable immune deficiency","volume":"176","author":"C Cunningham-Rundles","year":"2006","journal-title":"J Immunol"},{"issue":"3","key":"ref19","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1046\/j.1365-2362.2000.00619.x","article-title":"Decreased vitamin A levels in common variable immunodeficiency: vitamin A supplementation in vivo enhances immunoglobulin production and downregulates inflammatory responses","volume":"30","author":"P Aukrust","year":"2000","journal-title":"Eur J Clin Invest"},{"issue":"3","key":"ref20","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1007\/s10875-005-4090-6","article-title":"Vitamin a deficiency in patients with common variable immunodeficiency","volume":"25","author":"SS Kilic","year":"2005","journal-title":"J Clin Immunol"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/S0079-6603(08)60611-X","article-title":"DNA damage produced by ionizing radiation in mammalian cells: identities, mechanisms of formation, and reparability","volume":"35","author":"JF Ward","year":"1988","journal-title":"Prog Nucleic Acid Res Mol Biol"},{"issue":"37","key":"ref22","doi-asserted-by":"crossref","first-page":"5834","DOI":"10.1038\/sj.onc.1206682","article-title":"DNA damage checkpoint control in cells exposed to ionizing radiation","volume":"22","author":"G Iliakis","year":"2003","journal-title":"Oncogene"},{"issue":"3","key":"ref23","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1038\/85798","article-title":"DNA double-strand breaks: signaling, repair and the cancer connection","volume":"27","author":"KK Khanna","year":"2001","journal-title":"Nat Genet"},{"issue":"9","key":"ref24","doi-asserted-by":"crossref","DOI":"10.1101\/cshperspect.a012716","article-title":"DNA damage sensing by the ATM and ATR kinases","volume":"5","author":"A Marechal","year":"2013","journal-title":"Cold Spring Harb Perspect Biol"},{"key":"ref25","first-page":"33","article-title":"DNA-PK: the means to justify the ends?","volume":"99","author":"K Meek","year":"2008","journal-title":"Adv Immunol"},{"issue":"45","key":"ref26","doi-asserted-by":"crossref","first-page":"42462","DOI":"10.1074\/jbc.C100466200","article-title":"ATM phosphorylates histone H2AX in response to DNA double-strand breaks","volume":"276","author":"S Burma","year":"2001","journal-title":"J Biol Chem"},{"issue":"17","key":"ref27","doi-asserted-by":"crossref","first-page":"3717","DOI":"10.1016\/j.febslet.2010.05.021","article-title":"Focus on histone variant H2AX: to be or not to be","volume":"584","author":"J Yuan","year":"2010","journal-title":"FEBS Lett"},{"issue":"37","key":"ref28","doi-asserted-by":"crossref","first-page":"5774","DOI":"10.1038\/sj.onc.1206677","article-title":"P53 and radiation responses","volume":"22","author":"P Fei","year":"2003","journal-title":"Oncogene"},{"issue":"Pt 15","key":"ref29","doi-asserted-by":"crossref","first-page":"2527","DOI":"10.1242\/jcs.064501","article-title":"p53 at a glance","volume":"123","author":"CA Brady","year":"2010","journal-title":"J Cell Sci"},{"issue":"Suppl 1","key":"ref30","first-page":"1","article-title":"Primary immunodeficiency diseases. Report of an IUIS Scientific Committee. International Union of Immunological Societies","volume":"118","year":"1999","journal-title":"Clin Exp Immunol"},{"key":"ref31","first-page":"162","article-title":"Primary immunodeficiency diseases: an update on the classification from the international union of immunological societies expert committee for primary immunodeficiency","volume":"5","author":"W Al-Herz","year":"2014","journal-title":"Front Immunol"},{"issue":"6","key":"ref32","doi-asserted-by":"crossref","first-page":"2601","DOI":"10.4049\/jimmunol.1500250","article-title":"IRF4 Is a Critical Gene in Retinoic Acid-Mediated Plasma Cell Formation and Is Deregulated in Common Variable Immunodeficiency-Derived B Cells","volume":"195","author":"RL Indrevaer","year":"2015","journal-title":"J Immunol"},{"issue":"1","key":"ref33","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.radonc.2011.05.060","article-title":"The amount of DNA damage needed to activate the radiation-induced G2 checkpoint varies between single cells","volume":"101","author":"K Tkacz-Stachowska","year":"2011","journal-title":"Radiother Oncol"},{"issue":"3","key":"ref34","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1385\/MB:26:3:249","article-title":"The comet assay for DNA damage and repair: principles, applications, and limitations","volume":"26","author":"AR Collins","year":"2004","journal-title":"Mol Biotechnol"},{"issue":"10","key":"ref35","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1038\/nrc2716","article-title":"Tumour suppression by p53: a role for the DNA damage response?","volume":"9","author":"DW Meek","year":"2009","journal-title":"Nat Rev Cancer"},{"issue":"5","key":"ref36","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1038\/nrc3711","article-title":"Unravelling mechanisms of p53-mediated tumour suppression","volume":"14","author":"KT Bieging","year":"2014","journal-title":"Nat Rev Cancer"},{"issue":"51","key":"ref37","doi-asserted-by":"crossref","first-page":"36031","DOI":"10.1074\/jbc.274.51.36031","article-title":"Regulation of the p53 tumor suppressor protein","volume":"274","author":"M Oren","year":"1999","journal-title":"J Biol Chem"},{"issue":"4","key":"ref38","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1016\/j.cell.2009.04.050","article-title":"Modes of p53 regulation","volume":"137","author":"JP Kruse","year":"2009","journal-title":"Cell"},{"issue":"12","key":"ref39","doi-asserted-by":"crossref","first-page":"7666","DOI":"10.1093\/nar\/gku501","article-title":"Critical role for p53-serine 15 phosphorylation in stimulating transactivation at p53-responsive promoters","volume":"42","author":"J Loughery","year":"2014","journal-title":"Nucleic Acids Res"},{"issue":"3","key":"ref40","first-page":"305","article-title":"Gamma-H2AX\u2014a novel biomarker for DNA double-strand breaks","volume":"22","author":"LJ Kuo","year":"2008","journal-title":"In Vivo"},{"issue":"4","key":"ref41","doi-asserted-by":"crossref","first-page":"662","DOI":"10.4161\/cc.9.4.10764","article-title":"gammaH2AX foci analysis for monitoring DNA double-strand break repair: strengths, limitations and optimization","volume":"9","author":"M Lobrich","year":"2010","journal-title":"Cell Cycle"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"288","DOI":"10.3389\/fgene.2014.00288","article-title":"Comet assay to measure DNA repair: approach and applications","volume":"5","author":"A Azqueta","year":"2014","journal-title":"Front Genet"},{"issue":"4","key":"ref43","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1038\/cdd.2012.155","article-title":"A threshold mechanism mediates p53 cell fate decision between growth arrest and apoptosis","volume":"20","author":"M Kracikova","year":"2013","journal-title":"Cell Death Differ"},{"issue":"11","key":"ref44","doi-asserted-by":"crossref","first-page":"1847","DOI":"10.1002\/eji.1830181131","article-title":"Transcription of protooncogenes during stimulation of normal human B lymphocytes","volume":"18","author":"EB Smeland","year":"1988","journal-title":"Eur J Immunol"},{"issue":"11","key":"ref45","doi-asserted-by":"crossref","first-page":"3982","DOI":"10.1073\/pnas.83.11.3982","article-title":"Sequential expression of protooncogenes during lectin-stimulated mitogenesis of normal human lymphocytes","volume":"83","author":"JC Reed","year":"1986","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"8","key":"ref46","doi-asserted-by":"crossref","first-page":"1529","DOI":"10.1016\/j.freeradbiomed.2008.01.011","article-title":"ROS and p53: a versatile partnership","volume":"44","author":"B Liu","year":"2008","journal-title":"Free Radic Biol Med"},{"issue":"12","key":"ref47","doi-asserted-by":"crossref","first-page":"1306","DOI":"10.1038\/nm1320","article-title":"The antioxidant function of the p53 tumor suppressor","volume":"11","author":"AA Sablina","year":"2005","journal-title":"Nat Med"},{"issue":"9","key":"ref48","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1002\/cyto.a.20426","article-title":"Cytometry of ATM activation and histone H2AX phosphorylation to estimate extent of DNA damage induced by exogenous agents","volume":"71","author":"T Tanaka","year":"2007","journal-title":"Cytometry A"},{"issue":"21","key":"ref49","doi-asserted-by":"crossref","first-page":"3437","DOI":"10.1016\/j.febslet.2013.08.028","article-title":"gammaH2AX foci formation in the absence of DNA damage: mitotic H2AX phosphorylation is mediated by the DNA-PKcs\/CHK2 pathway","volume":"587","author":"WZ Tu","year":"2013","journal-title":"FEBS Lett"},{"issue":"7","key":"ref50","doi-asserted-by":"crossref","first-page":"3624","DOI":"10.4049\/jimmunol.1300213","article-title":"Retinoic acid improves defective TLR9\/RP105-induced immune responses in common variable immunodeficiency-derived B cells","volume":"191","author":"RL Indrevaer","year":"2013","journal-title":"J Immunol"},{"issue":"4","key":"ref51","doi-asserted-by":"crossref","first-page":"251","DOI":"10.3109\/08923973.2013.861481","article-title":"Safety of Toll-like receptor 9 agonists: a systematic review and meta-analysis","volume":"36","author":"M Qin","year":"2014","journal-title":"Immunopharmacol Immunotoxicol"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"22","DOI":"10.7603\/s40681-014-0022-1","article-title":"Retinoic acid and cancer treatment","volume":"4","author":"MC Chen","year":"2014","journal-title":"Biomedicine (Taipei)"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0185708","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,10,18]],"date-time":"2020-10-18T17:04:39Z","timestamp":1603040679000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0185708"}},"subtitle":[],"editor":[{"given":"Roberto","family":"Amendola","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2017,10,3]]},"references-count":52,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2017,10,3]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0185708","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,10,3]]}}}