Microenvironmental influences on human B-cell development

Immunol Rev. 2000 Jun;175:175-86.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

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

Substances

  • Calcium-Binding Proteins
  • Cytokines
  • Intercellular Signaling Peptides and Proteins
  • Interleukin-7
  • JAG1 protein, human
  • Jagged-1 Protein
  • Membrane Proteins
  • Receptors, Notch
  • Serrate-Jagged Proteins
  • flt3 ligand protein
  • thymic stromal lymphopoietin