In vitro identification of human pro-B cells that give rise to macrophages, natural killer cells, and T cells.

In this study we report the molecular and functional characterization of very early interleukin 7 receptor alpha (IL-7Ralpha)+-CD79a+CD19- B-cell progenitors, produced by human CD34+CD19-CD10- cord blood cells grown in the presence of stromal cells and cytokines. Purified IL-7Ralpha+CD79a+CD19- cells transcribed the B-lymphoid specific genes E2A, EBF, TdT, Rag-1, had initiated DJH rearrangements, but almost lacked Pax-5 mRNA. When exposed to appropriate environmental conditions, these cells repressed B-cell genes and completely differentiated into CD14+ macrophages, CD56+ natural killer cells, and CD4high T cells. Retention of the DJH rearranged genes in both CD14+ and CD56+ cells unambiguously demonstrates that early B-cell genes, expressed prior to Pax-5, can be activated in a multipotent human progenitor cell whose final fate, including in non-B lineages, is determined by external signals.