Microenvironmental influences on human B-cell development.

Mammalian B-cell development can be views 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 BCR0. Progression of cells through these checkpoints is profoundly influenced by the fetal liver and adult bone marrow (BM) stromal cell microenvironment. 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[sup+] hematopoeitic stem cells plated in 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 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. [ABSTRACT FROM AUTHOR]