Reversal of Blimp-1-mediated apoptosis by A1, a member of the Bcl-2 family.
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.
Knödel
M
M
Institute for Virology and Immunobiology, University of Würzburg, Würzburg, Germany.
Kuss
A W
AW
Lindemann
D
D
Berberich
I
I
Schimpl
A
A
D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D002454:Cell Differentiation; D002470:Cell Survival / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015536:Down-Regulation; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D018398:Homeodomain Proteins; D006801:Humans; D007144:Immunoglobulin J-Chains / Q000378:metabolism; D016393:Lymphoma, B-Cell; D051379:Mice; D015778:Minor Histocompatibility Antigens; D010641:Phenotype; D000074462:Positive Regulatory Domain I-Binding Factor 1; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D051818:Replication Protein C; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology*; D014407:Tumor Cells, Cultured
C096816:BCL2-related protein A1; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D007144:Immunoglobulin J-Chains; C096063:MATA1 protein, S cerevisiae; D015778:Minor Histocompatibility Antigens; C513258:Prdm1 protein, mouse; D019253:Proto-Oncogene Proteins c-bcl-2; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; C087042:PRDM1 protein, human; D000074462:Positive Regulatory Domain I-Binding Factor 1; D051818:Replication Protein C