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Bcl-2 expression promotes B- but not T-lymphoid development in scid mice

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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 immuno-globulin 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.

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Authors and Affiliations

  1. The Walter and Eliza Hall Institute of Medical Research, Post Office, Royal Melbourne Hospital, Victoria, 3050, Australia

    Andreas Strasser, Alan W. Harris, Lynn M. Corcoran & Suzanne Cory

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  1. Andreas Strasser
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  2. Alan W. Harris
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  3. Lynn M. Corcoran
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  4. Suzanne Cory
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Strasser, A., Harris, A., Corcoran, L. et al. Bcl-2 expression promotes B- but not T-lymphoid development in scid mice. Nature 368, 457–460 (1994). https://doi.org/10.1038/368457a0

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