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
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Apoptosis / immunology*
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Cell Differentiation
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Cell Survival / genetics
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Cell Survival / immunology
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Cells, Cultured
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / immunology*
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DNA-Binding Proteins / metabolism
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Down-Regulation
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Gene Transfer Techniques
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Genetic Vectors
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Homeodomain Proteins*
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Humans
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Immunoglobulin J-Chains / metabolism
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Lymphoma, B-Cell
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Mice
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Minor Histocompatibility Antigens
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Phenotype
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Positive Regulatory Domain I-Binding Factor 1
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Proto-Oncogene Proteins c-bcl-2 / genetics
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Proto-Oncogene Proteins c-bcl-2 / immunology*
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Proto-Oncogene Proteins c-bcl-2 / metabolism
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Replication Protein C
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Repressor Proteins*
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Saccharomyces cerevisiae Proteins*
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Transcription Factors / genetics
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Transcription Factors / immunology*
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Tumor Cells, Cultured
Substances
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BCL2-related protein A1
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DNA-Binding Proteins
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Homeodomain Proteins
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Immunoglobulin J-Chains
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MATA1 protein, S cerevisiae
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Minor Histocompatibility Antigens
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Prdm1 protein, mouse
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Proto-Oncogene Proteins c-bcl-2
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Repressor Proteins
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Saccharomyces cerevisiae Proteins
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Transcription Factors
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PRDM1 protein, human
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Positive Regulatory Domain I-Binding Factor 1
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Replication Protein C