Microenvironmental influences on human B-cell development.
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.
Bertrand
F E
FE
University of Minnesota Cancer Center, Minneapolis 55455, USA.
Eckfeldt
C E
CE
Fink
J R
JR
Lysholm
A S
AS
Pribyl
J A
JA
Shah
N
N
LeBien
T W
TW
D017209:Apoptosis; D001402:B-Lymphocytes / Q000276:immunology*; D001854:Bone Marrow Cells / Q000276:immunology*; D002135:Calcium-Binding Proteins; D002454:Cell Differentiation; D002455:Cell Division; D019070:Cell Lineage; D016207:Cytokines / Q000502:physiology; D005314:Embryonic and Fetal Development; D006412:Hematopoietic Stem Cells / Q000276:immunology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D015851:Interleukin-7 / Q000502:physiology; D000072100:Jagged-1 Protein; D008565:Membrane Proteins / Q000502:physiology; D008954:Models, Biological; D051880:Receptors, Notch; D000072099:Serrate-Jagged Proteins; D015398:Signal Transduction; D017154:Stromal Cells / Q000276:immunology*; D000094632:Thymic Stromal Lymphopoietin
D002135:Calcium-Binding Proteins; D016207:Cytokines; D036341:Intercellular Signaling Peptides and Proteins; D015851:Interleukin-7; C000606273:JAG1 protein, human; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; D051880:Receptors, Notch; D000072099:Serrate-Jagged Proteins; C084881:flt3 ligand protein; D000094632:Thymic Stromal Lymphopoietin