{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T12:33:16Z","timestamp":1789389196281,"version":"build-2803163510"},"reference-count":97,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2018,9,1]],"date-time":"2018-09-01T00:00:00Z","timestamp":1535760000000},"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":[[2018,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Malignant cell growth within patients with B cell chronic lymphocytic leukemia (B-CLL) is largely restricted to lymphoid tissues, particularly lymph nodes. The recent in vitro finding that TLR-9 ligand (oligodeoxynucleotide [ODN]) and IL-15 exhibit strong synergy in promoting B-CLL growth may be particularly relevant to growth in these sites. This study shows IL-15\u2013producing cells are prevalent within B-CLL\u2013infiltrated lymph nodes and, using purified B-CLL cells from blood, investigates the mechanism for ODN and IL-15 synergy in driving B-CLL growth. ODN boosts baseline levels of phospho-RelA(S529) in B-CLL and promotes NF-\u03baB\u2013driven increases in IL15RA and IL2RB mRNA, followed by elevated IL-15R\u03b1 and IL-2\/IL-15R\u03b2 (CD122) protein. IL-15\u2192CD122 signaling during a critical interval, 20 to 36\u201348 h following initial ODN exposure, is required for optimal induction of the cycling process. Furthermore, experiments with neutralizing anti\u2013IL-15 and anti-CD122 mAbs indicate that clonal expansion requires continued IL-15\/CD122 signaling during cycling. The latter is consistent with evidence of heightened IL2RB mRNA in the fraction of recently proliferated B-CLL cells within patient peripheral blood. Compromised ODN+IL-15 growth with limited cell density is consistent with a role for upregulated IL-15R\u03b1 in facilitating homotypic trans IL-15 signaling, although there may be other explanations. Together, the findings show that ODN and IL-15 elicit temporally distinct signals that function in a coordinated manner to drive B-CLL clonal expansion.<\/jats:p>","DOI":"10.4049\/jimmunol.1800591","type":"journal-article","created":{"date-parts":[[2018,8,1]],"date-time":"2018-08-01T15:15:34Z","timestamp":1533136534000},"page":"1570-1585","source":"Crossref","is-referenced-by-count":21,"title":["Mechanistic Insights into CpG DNA and IL-15 Synergy in Promoting B Cell Chronic Lymphocytic Leukemia Clonal Expansion"],"prefix":"10.1093","volume":"201","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5351-9223","authenticated-orcid":false,"given":"Rashmi","family":"Gupta","sequence":"first","affiliation":[{"name":"The Feinstein Institute for Medical Research, Northwell Health , Manhasset, NY 11030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3717-5803","authenticated-orcid":false,"given":"Xiao J","family":"Yan","sequence":"additional","affiliation":[{"name":"The Feinstein Institute for Medical Research, Northwell Health , Manhasset, NY 11030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline","family":"Barrientos","sequence":"additional","affiliation":[{"name":"Department of Medicine, North Shore University Hospital\u2013Long Island Jewish Medical Center, Northwell Health , Manhasset, NY 11303"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2700-4784","authenticated-orcid":false,"given":"Jonathan E","family":"Kolitz","sequence":"additional","affiliation":[{"name":"The Feinstein Institute for Medical Research, Northwell Health , Manhasset, NY 11030"},{"name":"Department of Medicine, North Shore University Hospital\u2013Long Island Jewish Medical Center, Northwell Health , Manhasset, NY 11303"},{"name":"Department of Medicine, Zucker School of Medicine at Hofstra\/Northwell , Hempstead, NY 11549"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3482-3182","authenticated-orcid":false,"given":"Steven L","family":"Allen","sequence":"additional","affiliation":[{"name":"The Feinstein Institute for Medical Research, Northwell Health , Manhasset, NY 11030"},{"name":"Department of Medicine, North Shore University Hospital\u2013Long Island Jewish Medical Center, Northwell Health , Manhasset, NY 11303"},{"name":"Department of Medicine, Zucker School of Medicine at Hofstra\/Northwell , Hempstead, NY 11549"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5804-2823","authenticated-orcid":false,"given":"Kanti","family":"Rai","sequence":"additional","affiliation":[{"name":"The Feinstein Institute for Medical Research, Northwell Health , Manhasset, NY 11030"},{"name":"Department of Medicine, North Shore University Hospital\u2013Long Island Jewish Medical Center, Northwell Health , Manhasset, NY 11303"},{"name":"Department of Medicine, Zucker School of Medicine at Hofstra\/Northwell , Hempstead, NY 11549"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"Chiorazzi","sequence":"additional","affiliation":[{"name":"The Feinstein Institute for Medical Research, Northwell Health , Manhasset, NY 11030"},{"name":"Department of Medicine, Zucker School of Medicine at Hofstra\/Northwell , Hempstead, NY 11549"},{"name":"Department of Molecular Medicine, Zucker School of Medicine at Hofstra\/Northwell , Hempstead, NY 11549"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4966-7741","authenticated-orcid":false,"given":"Patricia K A","family":"Mongini","sequence":"additional","affiliation":[{"name":"The Feinstein Institute for Medical Research, Northwell Health , Manhasset, NY 11030"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2018,9,1]]},"reference":[{"key":"2025030417572436300_r1","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1001\/jamaoncol.2015.0779","article-title":"Predicting prognosis in chronic lymphocytic leukemia in the contemporary era","volume":"1","author":"Nabhan","year":"2015","journal-title":"JAMA Oncol."},{"key":"2025030417572436300_r2","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/j.hoc.2013.01.002","article-title":"Biology of chronic lymphocytic leukemia in different microenvironments: clinical and therapeutic implications","volume":"27","author":"Herishanu","year":"2013","journal-title":"Hematol. 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