In vivo ablation of surface immunoglobulin on mature B cells by inducible gene targeting results in rapid cell death.
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.
Lam
K P
KP
Institute for Genetics, University of Cologne, Federal Republic of Germany.
Kühn
R
R
Rajewsky
K
K
D000818:Animals; D000954:Antigens, Surface / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D017209:Apoptosis / Q000276:immunology; D001402:B-Lymphocytes / Q000737:chemistry* / Q000166:cytology / Q000276:immunology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000276:immunology; D018390:Gene Targeting; D006412:Hematopoietic Stem Cells / Q000737:chemistry* / Q000166:cytology / Q000276:immunology; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D019426:Integrases / Q000494:pharmacology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D015513:Oncogene Proteins / Q000235:genetics; D010641:Phenotype; D011505:Protein-Tyrosine Kinases; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D051562:Proto-Oncogene Proteins c-bcr; D014162:Transfection; D014764:Viral Proteins
D000954:Antigens, Surface; D007143:Immunoglobulin Heavy Chains; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D014764:Viral Proteins; D011505:Protein-Tyrosine Kinases; C496614:Bcr protein, mouse; D051562:Proto-Oncogene Proteins c-bcr; C045073:Cre recombinase; D019426:Integrases