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A Three-dimensional Tissue Culture Model to Study Primary Human Bone Marrow and its Malignancies
Published on: March 8, 2014
Microenvironmental influences on human B-cell development
F E Bertrand1, C E Eckfeldt, J R Fink
1University of Minnesota Cancer Center, Minneapolis 55455, USA.
Immunological Reviews
|August 10, 2000
Summary
This study shows that human bone marrow stromal cells support B-cell development, guiding cells through key checkpoints and preventing apoptosis. Notch signaling may regulate this crucial B-cell maturation process.
Area of Science:
- Immunology
- Developmental Biology
- Cell Biology
Background:
- Mammalian B-cell development involves critical checkpoints, including B-cell lineage commitment and immunoglobulin gene rearrangement.
- The bone marrow (BM) microenvironment significantly influences B-cell maturation.
- Previous models often rely on transformed cell lines, limiting in vitro study of human B-cell development.
Purpose of the Study:
- To develop and validate an in vitro model of human B-cell development using non-transformed human BM stromal cells.
- To investigate the role of the human BM microenvironment in supporting B-cell lineage commitment and progression through developmental checkpoints.
- To explore the potential involvement of Notch signaling in human B-cell development.
Main Methods:
- Utilized freshly isolated, non-transformed human BM stromal cells as an in vitro microenvironment.
- Co-cultured human CD34+ hematopoietic stem cells with the human BM stromal cell microenvironment.
- Analyzed B-cell lineage commitment and progression through pre-B-cell receptor (pre-BCR) and B-cell receptor (BCR) checkpoints.
- Assessed cell survival and expression of Notch receptors and Jagged-1 ligand.
Main Results:
- Human CD34+ cells committed to the B-lineage and successfully navigated pre-BCR and BCR checkpoints within the human BM stromal cell microenvironment.
- The established microenvironment provided essential survival signals, inhibiting apoptosis in developing B-lineage cells.
- Differential expression of Notch receptors on B-lineage cells and Jagged-1 on stromal cells was observed, suggesting a role for Notch signaling.
Conclusions:
- Freshly isolated human BM stromal cells provide a functional microenvironment for in vitro human B-cell development.
- This model supports B-cell maturation through key checkpoints and promotes cell survival.
- Notch signaling is implicated as a potential regulator of human B-cell lineage commitment and checkpoint progression.
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