INTERLEUKIN-7 INDEPENDENT DEVELOPMENT OF HUMAN B-CELLS

Mammalian hematopoietic stem cell (HSC) commitment and differentiation into lymphoid lineage cells proceed through a series of developmental ly restricted progenitor compartments. A complete understanding of thi s process, and how it differs from HSC commitment and differentiation into cells of the myeloid/erythroid lineages, requires the development of model systems that support HSC commitment to the lymphoid lineages , We now describe a human bone marrow stromal cell culture that prefer entially supports commitment and differentiation of human HSC to CD19( +) B-lineage cells, Fluorescence activated cell sorter-purified CD34(+)/lineage(-) cells were isolated from fetal bone marrow and cultured on human fetal bone marrow stromal cells in serum-free conditions cont aining no exogenous cytokines, Over a period of 3 weeks, CD34(++)/line age(-) cells underwent commitment, differentiation, and expansion into the B lineage, Progressive changes included: loss of CD34, acquisitio n of and graded increases in the level of cell surface CD19, and appea rance of immature B cells expressing mu/kappa or mu/lambda cell surfac e fg receptors, The tempo and phenotype of B-cell development was not influenced by the addition of IL-7 (10 ng/ml), or by the addition of g oat anti-IL-7 neutralizing antibody. These results indicate a profound difference between mouse and human in the requirement for IL-7 in nor mal B-cell development, and provide an experimental system to identify and characterize human bone marrow stromal cell-derived molecules cru cial for human B lymphopoiesis.