Differentiation of B lymphocytes from hematopoietic stem cells.

Differentiation of B lymphocytes can be efficiently obtained when multipotent hematopoietic precursors are cocultured with stromal cell lines and soluble growth factors. Stromal cell lines provide yet-undefined signals required for the expansion of the precursor population and/or lineage commitment and soluble mediators. In consequence, the type of the exogenously added interleukins depends on the stromal support used in the assay. In contrast to S17 and OP9 stroma, the fibroblast line NIH3T3 does not support B-cell precursor expansion of CD19(+) fetal liver cells; neither does it induce B-lineage differentiation from embryonic multipotent progenitors, in the absence of added cytokines. Under these conditions c-kit ligand, interleukin-7 (IL-7), and Flt3 ligand (Flt3-L) are added to the cultures to ensure optimal B-cell differentiation. Another cytokine, stroma-derived lymphopoietin, can also be used instead of IL-7 in embryonic but not adult hematopoietic precursors.