BCL-2 EXPRESSION PROMOTES B-LYMPHOID BUT NOT T-LYMPHOID DEVELOPMENT IN SCID MICE
- Author(s)
- Strasser, A; Harris, AW; Corcoran, LM; Cory, S;
- Details
- Publication Year 1994-03-31,Volume 368,Issue #6470,Page 457-460
- Journal Title
- NATURE
- Publication Type
- Journal Article
- Abstract
- EXPRESSION of antigen receptors is vital for the development of B and T lymphocytes. In mice with the scid mutation1,2, which are unable to make productive rearrangements of their immunoglobulin and T-cell receptor (TCR) genes, lymphopoiesis aborts at an early stage. The death of the immature lymphocytes by apoptosis3 is postulated to result from a failure to receive a survival signal induced by receptor engagement4. Consistent with this hypothesis, introduction of immunoglobulin or TCR transgenes into scid mice promoted an increase in B- or T-lymphoid cells, respectively5-7. As the protein encoded by the bcl-2 gene can inhibit cell death8,9, we tested whether lymphopoiesis could be rescued in scid mice by crossing in a bcl-2 transgene. Strikingly, the bcl-2/scid mice accumulated almost normal numbers of B-lymphoid cells which lacked surface immunoglobulin but expressed markers of maturity. T-cell development remained blocked. Introducing a TCR transgene enabled bcl-2/scid mice to develop normal numbers of CD4+8+ thymocytes even in the absence of immunological selection, suggesting that T cells become competent to respond to bcl-2 protein only after the TCR complex is displayed at the cell surface.
- Publisher
- MACMILLAN MAGAZINES LTD
- Keywords
- TRANSGENIC MICE; CELL-RECEPTOR; BONE-MARROW; MOUSE; SURVIVAL; ACTIVATION; APOPTOSIS
- Publisher's Version
- https://doi.org/10.1038/368457a0
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 1994-03-31 12:00:00