Microenvironmental influences on human B-cell development

被引:25
作者
Bertrand, FE [1 ]
Eckfeldt, CE [1 ]
Fink, JR [1 ]
Lysholm, AS [1 ]
Pribyl, JAR [1 ]
Shah, N [1 ]
LeBien, TW [1 ]
机构
[1] Univ Minnesota, Ctr Canc, Minneapolis, MN 55455 USA
关键词
D O I
10.1034/j.1600-065X.2000.017513.x
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Mammalian B-cell development can be viewed as a developmental performance with several acts. The acts are represented by check-points 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.
引用
收藏
页码:175 / 186
页数:12
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