Mammalian B‐cell development can be viewed as a developmental performance with several acts. The acts are represented by checkpoints centered around commitment to the B‐lineage and functional Ig gene rearrangement – culminating in expression of the pre‐B‐cell receptor (pre‐BCR) and the BCR. Progression of cells through these checkpoints is profoundly influenced by the fetal liver and adult bone marrow (BM) stromal cell microenvironments. Our laboratory has developed a model of human B‐cell development that utilizes freshly isolated/non‐transformed human BM stromal cells as an in vitro microenvironment. Human CD34+ hematopoietic stem cells plated in this human BM stromal cell microenvironment commit to the B lineage and progress through the pre‐BCR and BCR checkpoints. This human BM stromal cell microenvironment also provides survival signals that prevent apoptosis in human B‐lineage cells. Human B‐lineage cells exhibit differential expression of Notch receptors and human BM stromal cells express the Notch ligand Jagged‐1. These results suggest a potential role for Notch in regulating B‐lineage commitment and/or progression through the pre‐BCR and BCR checkpoints.