Repression of c-myc is necessary but not sufficient for terminal differentiation of B lymphocytes in vitro.
The importance of c-myc as a target of the Blimp-1 repressor has been studied in BCL-1 cells, in which Blimp-1 is sufficient to trigger terminal B-cell differentiation. Our data show that Blimp-1-dependent repression of c-myc is required for BCL-1 differentiation, since constitutive expression of c-Myc blocked differentiation. Furthermore, ectopic expression of cyclin E mimicked the effects of c-Myc on both proliferation and differentiation, indicating that the ability of c-Myc to drive proliferation is responsible for blocking BCL-1 differentiation. However, inhibition of c-Myc by a dominant negative form was not sufficient to drive BCL-1 differentiation. Thus, during Blimp-1-dependent plasma cell differentiation, repression of c-myc is necessary but not sufficient, demonstrating the existence of additional Blimp-1 target genes.
Lin
K I
KI
Department of Microbiology, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA.
Lin
Y
Y
Calame
K
K
D001402:B-Lymphocytes / Q000166:cytology*; D002454:Cell Differentiation; D019927:Cyclin E / Q000378:metabolism; D016207:Cytokines / Q000494:pharmacology; D005786:Gene Expression Regulation; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D007075:Immunoglobulin M / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D008954:Models, Biological; D009154:Mutation; D010950:Plasma Cells / Q000166:cytology; D011509:Proteoglycans / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D012097:Repressor Proteins / Q000378:metabolism*; D053667:Syndecans; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D019927:Cyclin E; D016207:Cytokines; D000949:Histocompatibility Antigens Class II; D007075:Immunoglobulin M; D008562:Membrane Glycoproteins; D011509:Proteoglycans; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D012097:Repressor Proteins; D053667:Syndecans; D014157:Transcription Factors