Reversal of Blimp-1-mediated apoptosis by A1, a member of the Bcl-2 family

Eur J Immunol. 1999 Sep;29(9):2988-98. doi: 10.1002/(SICI)1521-4141(199909)29:09<2988::AID-IMMU2988>3.0.CO;2-T.

Abstract

Blimp-1 (B lymphocyte-induced maturation protein 1) is strongly expressed during the late stages of B cell differentiation to immunoglobulin-secreting plasma cells. Overexpression of Blimp-1 in B lymphoma cells has been reported to induce either growth arrest and cell death or Ig secretion and terminal differentiation, depending on the developmental stage of the recipient lymphomas. By using a retroviral expression system we show that Blimp-1-transduced immature WEHI 231 murine B lymphoma cells produce J chain, increased levels of the secretory form of micro heavy chain mRNA and secrete IgM for a short period of time. Concomitantly, they exhibit altered ratios of c-myc/mad4 mRNA levels, a reduction in the expression of the anti-apoptotic bcl-2 family member A1 and a distinct growth disadvantage, followed by cell death. Reintroduction of A1 by retroviral transduction greatly extends the life span of Blimp-1-expressing WEHI 231 cells which continue to secrete IgM. These data suggest that levels of A1 may determine the checkpoint between death and survival of Blimp-1-expressing B cells at different stages of differentiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / immunology*
  • Cell Differentiation
  • Cell Survival / genetics
  • Cell Survival / immunology
  • Cells, Cultured
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / immunology*
  • DNA-Binding Proteins / metabolism
  • Down-Regulation
  • Gene Transfer Techniques
  • Genetic Vectors
  • Homeodomain Proteins*
  • Humans
  • Immunoglobulin J-Chains / metabolism
  • Lymphoma, B-Cell
  • Mice
  • Minor Histocompatibility Antigens
  • Phenotype
  • Positive Regulatory Domain I-Binding Factor 1
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / immunology*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Replication Protein C
  • Repressor Proteins*
  • Saccharomyces cerevisiae Proteins*
  • Transcription Factors / genetics
  • Transcription Factors / immunology*
  • Tumor Cells, Cultured

Substances

  • BCL2-related protein A1
  • DNA-Binding Proteins
  • Homeodomain Proteins
  • Immunoglobulin J-Chains
  • MATA1 protein, S cerevisiae
  • Minor Histocompatibility Antigens
  • Prdm1 protein, mouse
  • Proto-Oncogene Proteins c-bcl-2
  • Repressor Proteins
  • Saccharomyces cerevisiae Proteins
  • Transcription Factors
  • PRDM1 protein, human
  • Positive Regulatory Domain I-Binding Factor 1
  • Replication Protein C