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

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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Heinig K, Gätjen M, Grau M, Stache V, Anagnostopoulos I, Gerlach K, Niesner RA, Cseresnyes Z, Hauser AE, Lenz P, Hehlgans T, Brink R, Westermann J, Dörken B, Lipp M, Lenz G, Rehm A, Höpken UE