B cells promote tumor angiogenesis by enhancing endothelial cell function in a Stat3-dependent manner.

<p>(<b>A</b>) Representative images of vessel formation in Matrigel plugs implanted in <i>Rag1^−/−</i> mice. The Matrigel plugs contain either B16 tumor cell alone, <i>Stat3^+/+</i> B cell alone or B16 tumor cells plus <i>Stat3^+/+</i> or <i>Stat3</i>^−/− B cells, which were isolated from splenocytes of tumor-bearing mice; <i>n</i> = 5; area indicated by blue dot showing level of blood vessel formation. (<b>B</b>) Hemoglobin contents in the pooled Matrigel plugs determined by colorimetric assay; means ± SEM, <i>n</i> = 5. (<b>C</b>) <i>In vitro</i> collagen tube formation assay showing the number of tubes formed by ECs with or without the indicated B cells. <i>Stat3^+/+</i> B cells were enriched from splenocytes of B16 tumor-bearing mice (left) or B16 tumors (right); means ± SEM, <i>n</i> = 3. (<b>D</b>) B cell-mediated endothelial cell tube formation requires Stat3 signaling in B cells. EC tube formation by co-culturing ECs with tumor-primed <i>Stat3^+/+</i> or <i>Stat3^−/−</i> splenic B cells. Tumor-primed B cells were enriched from splenocytes of MB49 tumor-bearing mice with <i>Stat3^+/+</i> or <i>Stat3^−/−</i> hematopoietic cells; means ± SEM, <i>n</i> = 3; ****, <i>P</i><0.0001.