Microenvironmental influences on human B-cell development.

F E Bertrand, C E Eckfeldt, J R Fink, A S Lysholm, J A Pribyl, N Shah, T W LeBien

Journal: Immunological reviews 2000;175():175-86

PMID: 10933602

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Abstract

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.

Address: University of Minnesota Cancer Center, Minneapolis 55455, USA.

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MeSH Terms: Apoptosis, B-Lymphocytes, Bone Marrow Cells, Calcium-Binding Proteins, Cell Differentiation, Cell Division, Cell Lineage, Cytokines, Embryonic and Fetal Development, Hematopoietic Stem Cells, Humans, Intercellular Signaling Peptides and Proteins, Interleukin-7, Jagged-1 Protein, Membrane Proteins, Models, Biological, Receptors, Notch, Serrate-Jagged Proteins, Signal Transduction, Stromal Cells, Thymic Stromal Lymphopoietin