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Accession IconGSE60925

Access to follicular dendritic cells is a pivotal step in murine chronic lymphocytic leukemia B cell activation and proliferation

Organism Icon Mus musculus
Sample Icon 18 Downloadable Samples
Technology Badge Icon Affymetrix Mouse Gene 1.1 ST Array (mogene11st)

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In human chronic lymphocytic leukemia (CLL) pathogenesis B cell antigen receptor signaling seems important for leukemia B cell ontogeny, whereas the microenvironment influences B cell activation, tumor cell lodging and provision of antigenic stimuli. Using the murine E-Tcl1 CLL model, we demonstrate that CXCR5-controlled access to follicular dendritic cells (FDCs) confers proliferative stimuli to leukemia B cells. Intravital imaging revealed a marginal zone B cell-like leukemia cell trafficking route. Murine and human CLL cells reciprocally stimulated resident mesenchymal stromal cells through lymphotoxin--receptor activation, resulting in CXCL13 secretion and stromal compartment remodeling. Inhibition of lymphotoxin/lymphotoxin--receptor signaling or of CXCR5 signaling retards leukemia progression. Thus, CXCR5 activity links tumor cell homing, shaping a survival niche, and access to localized proliferation stimuli.
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