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Reversion of B cell commitment upon loss of Pax5 expression
Ingvild Mikkola1, Barry Heavey, Markus Horcher
1Research Institute of Molecular Pathology, Vienna Biocenter, Dr. Bohr-Gasse 7, A-1030 Vienna, Austria.
Science (New York, N.Y.)
|July 6, 2002
Summary
The transcription factor Pax5 is crucial for B cell development. Its continuous expression is required to maintain B cell commitment, preventing early B cells from becoming other blood cell types.
Area of Science:
- Immunology
- Developmental Biology
- Hematopoiesis
Background:
- The transcription factor Pax5 initiates B cell lineage commitment.
- The role of Pax5 in maintaining B cell commitment is not well understood.
Purpose of the Study:
- To investigate the role of Pax5 in maintaining B cell lineage commitment during early development.
- To determine if Pax5 is continuously required for B cell identity.
Main Methods:
- Conditional inactivation of the Pax5 gene in committed pro-B cells.
- In vitro differentiation assays to assess macrophage potential.
- In vivo reconstitution assays in RAG2-/- mice to evaluate T cell development capacity.
Main Results:
- Conditional Pax5 inactivation in pro-B cells led to the loss of B cell transcription program initiation and maintenance.
- Pax5-deficient pro-B cells regained the ability to differentiate into macrophages in vitro.
- These cells could also reconstitute T cell development in vivo in RAG2-/- mice.
Conclusions:
- Pax5 expression is continuously required to maintain B cell lineage commitment.
- Loss of Pax5 converts committed pro-B cells into hematopoietic progenitors with multilineage potential.
- Pax5 is essential for maintaining B cell identity throughout early development.
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