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Bcl-2 expression promotes B- but not T-lymphoid development in scid mice
A Strasser1, A W Harris, L M Corcoran
1Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Victoria, Australia.
Nature
|March 31, 1994
Summary
The bcl-2 gene promotes B and T lymphocyte survival in scid mice by preventing apoptosis. Introducing a bcl-2 transgene rescues B-cell development, but T-cell development requires T-cell receptor expression.
Area of Science:
- Immunology
- Developmental Biology
- Molecular Biology
Background:
- Lymphocyte development relies on antigen receptor expression for survival signals.
- Severe combined immunodeficiency (SCID) mutation prevents lymphocyte development due to failed gene rearrangements.
- Apoptosis (programmed cell death) is implicated in the developmental block in SCID lymphocytes.
Purpose of the Study:
- To investigate if the anti-apoptotic bcl-2 gene could rescue lymphopoiesis in SCID mice.
- To determine the role of bcl-2 in lymphocyte development and survival.
- To explore the interplay between receptor expression and bcl-2 mediated survival.
Main Methods:
- Crossed bcl-2 transgenic mice with SCID mice to create bcl-2/SCID mice.
- Analyzed B and T lymphocyte populations in bcl-2/SCID mice.
- Introduced T-cell receptor (TCR) transgenes into bcl-2/SCID mice to assess T-cell development.
Main Results:
- bcl-2/SCID mice showed a significant increase in B-lymphoid cells, nearing normal numbers, though lacking surface immunoglobulin.
- T-cell development remained blocked in bcl-2/SCID mice.
- Introduction of a TCR transgene in bcl-2/SCID mice allowed for the development of CD4+8+ thymocytes, even without selection.
Conclusions:
- The bcl-2 gene can rescue B-lymphopoiesis in SCID mice by inhibiting apoptosis.
- T-cell development is dependent on T-cell receptor expression for bcl-2 to mediate survival.
- Antigen receptor expression is critical for both lymphocyte development and the efficacy of anti-apoptotic mechanisms.
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