Access to follicular dendritic cells is a pivotal step in murine chronic lymphocytic leukemia B cell activation and proliferation
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ABSTRACT: 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
ORGANISM(S): Mus musculus
SUBMITTER: Michael Grau
PROVIDER: E-GEOD-60925 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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