Abstract
Gene targeting experiments have demonstrated that the expression of immunoglobulin heavy chain in the pre-B cell receptor (pBCR) and of heavy and light chains in the B cell antigen receptor (BCR) marks checkpoints in early B cell development that the cells have to pass to survive. To investigate whether the persistence of mature B cells in the peripheral immune system also depends on BCR expression, we have generated a transgenic mouse in which the BCR can be inducibly ablated through V region gene deletion. Ablation leads to rapid death of mature B lymphocytes, which is preceded by down-regulation of MHC antigens and up-regulation of CD95 (Fas) and can be delayed by constitutive bcl-2 expression.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antigens, Surface / chemistry
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Antigens, Surface / genetics
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Antigens, Surface / immunology
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Apoptosis / immunology
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B-Lymphocytes / chemistry*
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B-Lymphocytes / cytology
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B-Lymphocytes / immunology
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Cell Differentiation / genetics
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Cell Differentiation / immunology
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Female
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Flow Cytometry
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Gene Deletion
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Gene Expression Regulation, Developmental / drug effects
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Gene Expression Regulation, Developmental / immunology
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Gene Targeting*
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Hematopoietic Stem Cells / chemistry*
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Hematopoietic Stem Cells / cytology
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Hematopoietic Stem Cells / immunology
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Immunoglobulin Heavy Chains / genetics*
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Integrases / pharmacology
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Male
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Mice
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Mice, Transgenic
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Oncogene Proteins / genetics
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Phenotype
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Protein-Tyrosine Kinases*
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Proto-Oncogene Proteins c-bcl-2 / genetics
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Proto-Oncogene Proteins c-bcr
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Proto-Oncogene Proteins*
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Transfection
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Viral Proteins*
Substances
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Antigens, Surface
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Immunoglobulin Heavy Chains
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Oncogene Proteins
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-bcl-2
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Viral Proteins
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Protein-Tyrosine Kinases
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Bcr protein, mouse
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Proto-Oncogene Proteins c-bcr
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Cre recombinase
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Integrases