By investigating the germinal center (GC) formation in STAT6ko/WT bone marrow-mixed chimera we found that GC formation in type 2 immune responses is dependent on B cell intrinsic expression of IL-4/IL-13-induced genes. We therefore used microarrays to find Stat6 dependent genes that are important for germinal center formation and/or organization after infection with the nematode Nippostrongylus brasiliensis (N. brasiliensis).
B-cell-intrinsic STAT6 signaling controls germinal center formation.
Specimen part
View SamplesIn 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.
Access to follicular dendritic cells is a pivotal step in murine chronic lymphocytic leukemia B-cell activation and proliferation.
Specimen part
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