Related Experiment Videos
Fidelity and infidelity in commitment to B-lymphocyte lineage development.
A G Rolink1, C Schaniel, M Busslinger
1Basel Institute for Immunology, Switzerland. Rolink@bii.ch
Immunological Reviews
|August 10, 2000
Summary
Pax-5-deficient pre-B I cells exhibit remarkable plasticity, differentiating into myeloid and T-cell lineages instead of B cells. These cells can reconstitute T-cell compartments and thymus development in RAG-deficient hosts, highlighting their multipotent potential.
Area of Science:
- Immunology
- Developmental Biology
- Cell Biology
Background:
- B-lymphocyte development involves distinct stages, including pre-B I cells expressing specific B-lineage genes and immunoglobulin heavy chain rearrangements.
- Wild-type pre-B I cells are committed to B-lineage differentiation, reconstituting B-cell compartments but not T-lineage or myeloid cells.
- Pax-5 is crucial for B-lymphocyte development, with its deficiency arresting development at the pre-B I to pre-B II transition.
Purpose of the Study:
- To investigate the differentiation potential of Pax-5-deficient pre-B I cells.
- To determine if Pax-5-deficient pre-B I cells can reconstitute lymphoid compartments in RAG-deficient hosts.
- To explore the plasticity and lineage commitment of pre-B I cells.
Main Methods:
- Transplantation of wild-type and Pax-5-deficient pre-B I cells into RAG-deficient mouse hosts.
- In vitro culture of Pax-5-deficient pre-B I cells with various cytokines (IL-7, M-CSF, GM-CSF) and stromal cells.
- Analysis of cell surface markers, gene expression, and lymphoid reconstitution in transplanted hosts.
Main Results:
- Pax-5-deficient pre-B I cells, unlike wild-type cells, differentiate into macrophages, dendritic cells, granulocytes, and osteoclasts in vitro.
- Transplantation of Pax-5-deficient pre-B I cells into RAG-deficient hosts leads to full reconstitution of the thymus and T-cell compartments, but not B cells.
- Pax-5-deficient pre-B I cells demonstrate long-term reconstituting potential and can home to the bone marrow, showing plasticity beyond the B-cell lineage.
Conclusions:
- Pax-5 deficiency unmasks a latent multipotent potential in pre-B I cells, allowing differentiation into myeloid and T-cell lineages.
- The expression of certain B-lineage genes (Ig alpha, Igbeta, VpreB, lambda5) in thymocytes does not represent irreversible commitment to the B lineage.
- Pre-B I cells possess significant plasticity and can serve as long-term reconstituting cells for T-cell development under specific conditions.