Human cord blood, but not adult bone marrow, gives rise to IL-7-independent B cell production

IL-7 is critical for B cell production in adult mice, however its role in human B lymphopoiesis is controversial. Using a novel, human-only culture model we show that IL-7 increases human B cell production by >60-fold from hematopoietic stem cells (HSCs) in both cord blood (CB) and adult bone marrow (BM). IL-7-induced increases are dose-dependent and specific to CD19+ cells. STAT5 phosphorylation and expression of the Ki-67 proliferation antigen indicate that IL-7 acts directly on CD19+ cells to increase proliferation at the CD34+ and CD34- pro-B cell stages, but not among CD19- B lineage precursors. As compared to CB, adult BM shows a reduction of  in vitro  generative capacity that is progressively more profound in developmentally sequential B cell precursor populations, resulting in a ~50-fold reduction in IL-7-dependent B lineage generative capacity. Without IL-7, HSCs in CB, but not BM, give rise to a small but consistent population of CD19 LO  B lineage cells that express EBF and PAX-5 and respond to subsequent IL-7 stimulation. Flt3 ligand, but not TSLP, was required for the IL-7-independent production of human B lineage cells. These data provide evidence that human B cell production from adult BM is dependent on IL-7 and suggest that a mechanism in addition to the "developmental switch" observed in the mouse model may be responsible for IL-7 dependency in adult human B lymphopoiesis.