IL-7 is required for B cell development from adult human bone marrow due to decreased B lymphoid generative capacity

Human B lymphopoiesis is thought to differ from that in mouse with respect to the requirement for IL-7. Here we investigated the role of IL-7 in human B cell development using an  in vitro  model based on co-culturing human hematopoietic stem cells (HSCs) on primary stroma from adult human bone marrow (BM). Addition of IL-7 to this co-culture model increased B cell production by ∼40-fold. IL-7-induced increases were dose-dependent and specific to CD19+ cells. Flow cytometry analysis of STAT5 phosphorylation, IL-7Rα, and the proliferation antigen, ki-67, indicate that IL-7 acts directly on B cell precursors where it increases proliferation, but not cell survival. The effects of IL-7 were most profound in cultures with adult BM HSCs where few, if any, human B lineage cells are generated in the absence of IL-7 activity. When co-cultures initiated with cord blood (CB) and BM HSCs were compared, IL-7-induced increases were similar in magnitude, and B cell precursors responded similarly to IL-7. However, a comparison of the generative capacity of CB and BM HSCs showed that the ability of BM HSCs to give rise to CD19+, but not CD19− cells, was 40 times less than that of CB HSCs. Our results provide evidence that IL-7 is critical for B cell production from HSCs in adult BM due to their low B lymphoid generative capacity as compared to HSCs in CB.