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

Nature. 1994 Mar 31;368(6470):457-60. doi: 10.1038/368457a0.

Abstract

Expression of antigen receptors is vital for the development of B and T lymphocytes. In mice with the scid mutation, 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 apoptosis is postulated to result from a failure to receive a survival signal induced by receptor engagement. Consistent with this hypothesis, introduction of immunoglobulin or TCR transgenes into scid mice promoted an increase in B- or T-lymphoid cells, respectively. As the protein encoded by the bcl-2 gene can inhibit cell death, 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigens, Differentiation / biosynthesis
  • B-Lymphocytes / cytology*
  • Base Sequence
  • Bone Marrow Cells
  • Cell Differentiation
  • Cell Survival
  • Cells, Cultured
  • DNA Primers
  • Immunophenotyping
  • Mice
  • Mice, SCID
  • Mice, Transgenic
  • Molecular Sequence Data
  • Proto-Oncogene Proteins / biosynthesis*
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins c-bcl-2
  • Receptors, Antigen, B-Cell / biosynthesis
  • Receptors, Antigen, T-Cell / biosynthesis
  • Spleen / cytology
  • T-Lymphocytes / cytology*

Substances

  • Antigens, Differentiation
  • DNA Primers
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Receptors, Antigen, B-Cell
  • Receptors, Antigen, T-Cell