{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,5,30]],"date-time":"2026-05-30T04:05:47Z","timestamp":1780113947004,"version":"3.54.0"},"posted":{"date-parts":[[2024,11,17]]},"group-title":"Pathology","reference-count":78,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2024,11,17]],"date-time":"2024-11-17T00:00:00Z","timestamp":1731801600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,5,27]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Adaptive immune responses occur lymph nodes (LNs) in a microenvironment established by resident stromal cells. LNs are also a site of proliferation of chronic lymphocytic leukemia (CLL), a B cell cancer that alters LN structure in a stereotypic manner. To deeply characterize reactive and CLL LNs, we developed a single-cell RNA sequencing pipeline. We find that proliferation of CLL cells in proliferation centers (PCs), a CLL-specific niche, begins with transient upregulation of\n                  <jats:italic>MYC,<\/jats:italic>\n                  subsequent downregulation of which may limit CLL growth. PCs contain a distinct fibroblast population expressing\n                  <jats:italic>CCL19<\/jats:italic>\n                  while CLL cells express the CCL19 receptor CCR7, providing a recruitment mechanism for CLL cells to PCs. Using informatic, spatial, and in situ analyses to identify ligand-receptor pairs involving PC CLL cells and nearby immune and stromal cells, we observe that PCs are enriched for macrophages expressing BAFF, the integrin \u03b1X\u03b22 heterodimer, and Galectin9, factors implicated in cell growth, adhesion, and immunosuppression. The most common predicted interactions in PCs involve CD74 and ligands such as MIF, and we find that CD74 blockade consistently inhibits CLL cell growth in culture. Our work highlights key features of the CLL proliferative niche and provides a roadmap for identifying vulnerabilities and new therapeutic strategies.\n                <\/jats:p>","DOI":"10.1101\/2024.11.15.623868","type":"posted-content","created":{"date-parts":[[2024,11,17]],"date-time":"2024-11-17T23:45:19Z","timestamp":1731887119000},"source":"Crossref","is-referenced-by-count":0,"title":["CCL19\u207a fibroblasts define a proliferative niche in chronic lymphocytic leukemia"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4614-8580","authenticated-orcid":false,"given":"Antonio P.","family":"Ferreira","sequence":"first","affiliation":[{"name":"Department of Pathology, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, Massachusetts, USA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shumei","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pathology, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, Massachusetts, USA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larysa","family":"Poluben","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, Cancer Research Institute, Beth Israel Deaconess Medical Center, Boston, Massachusetts. USA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominique","family":"Morais","sequence":"additional","affiliation":[{"name":"Department of Pathology, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, Massachusetts, USA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua","family":"Brandstadter","sequence":"additional","affiliation":[{"name":"Department of Medicine, Perlman Cancer Center, University of Pennsylvania Medical School, Philadelphia, Pennsylvania, USA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Perkey","sequence":"additional","affiliation":[{"name":"Department of Medicine, Section of Hematology\/Oncology, University of Chicago Medical School, Chicago, Illinois, USA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Sotirakos","sequence":"additional","affiliation":[{"name":"Department of Pathology, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, Massachusetts, USA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mai","family":"Drew","sequence":"additional","affiliation":[{"name":"Department of Pathology, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, Massachusetts, USA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Pathology, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, Massachusetts, USA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madeleine E.","family":"Lemieux","sequence":"additional","affiliation":[{"name":"Bioinfo, Plantagenet, Ontario, Canada;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stacey M","family":"Fernandes","sequence":"additional","affiliation":[{"name":"Chronic Lymphocytic Leukemia (CLL) Center, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, United States;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David M.","family":"Dorfman","sequence":"additional","affiliation":[{"name":"Department of Pathology, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, Massachusetts, USA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brent","family":"Shoji","sequence":"additional","affiliation":[{"name":"Department of Surgery, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, Massachusetts, USA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean R.","family":"Stowell","sequence":"additional","affiliation":[{"name":"Department of Pathology, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, Massachusetts, USA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"Maillard","sequence":"additional","affiliation":[{"name":"Department of Medicine, Perlman Cancer Center, University of Pennsylvania Medical School, 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