Overexpression of c-Fos induces apoptosis of CD43+ pro-B cells.
The proto-oncogene product c-Fos, a component of the transcription factor AP-1, is induced in early B lineage cells. To investigate a role of c-Fos in early B cell development, fetal liver (FL) cells from transgenic mice carrying an IFN-alphabeta (IFN)-inducible c-fos gene (Mx-c-fosD) were cultured on a stromal cell layer with IL-7. Although B lineage cells normally developed in the Mx-c-fosD FL cell culture, the development was perturbed by the addition of IFN at the beginning of culture. When IFN was added in the FL culture after B lineage cells developed, pro-B (B220+,CD43+) cells were selectively dying by apoptosis within 48 h after IFN stimulation. This apoptosis was intrinsically induced in the pro-B cells that overexpressed c-fos when the Mx-c-fosD FL (H-2Kb) cells were cocultured with the normal C3H FL (H-2Kk) cells. The molecular basis of the apoptosis was investigated by examining expression of the genes that regulate apoptosis. The IFN stimulation did not modulate expression of Bcl-2 and Fas in early B lineage cells from the Mx-c-fosD FL culture. However, Rag-2 was down-regulated in these cells within 12 h after IFN stimulation. These results suggest that the c-Fos plays a causal role in deletion of pro-B cells with nonfunctional Ag receptor.
Hu
L
L
Center for Biomedical Science, Chiba University School of Medicine, Japan.
Hatano
M
M
Rüther
U
U
Tokuhisa
T
T
D000818:Animals; D015703:Antigens, CD; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics*; D001402:B-Lymphocytes / Q000166:cytology* / Q000187:drug effects; D001854:Bone Marrow Cells; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D018920:Coculture Techniques; D003238:Connective Tissue / Q000502:physiology; D004268:DNA-Binding Proteins; D019204:GTP-Binding Proteins; D005786:Gene Expression Regulation / Q000187:drug effects; D016762:Genes, fos; D006183:H-2 Antigens / Q000276:immunology; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000276:immunology; D016898:Interferon-alpha / Q000494:pharmacology; D015851:Interleukin-7 / Q000494:pharmacology; D051917:Leukosialin; D008099:Liver / Q000166:cytology / Q000196:embryology; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D064547:Myxovirus Resistance Proteins; D011401:Promoter Regions, Genetic / Q000187:drug effects; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000235:genetics; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis*; D011947:Receptors, Antigen, B-Cell / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D012795:Sialoglycoproteins / Q000032:analysis*; D019014:fas Receptor / Q000096:biosynthesis / Q000235:genetics
D015703:Antigens, CD; D004268:DNA-Binding Proteins; D006183:H-2 Antigens; C024755:H-2K(K) antigen; C032876:H-2Kb protein, mouse; D016898:Interferon-alpha; D015851:Interleukin-7; D051917:Leukosialin; C579070:Mx1 protein, mouse; D064547:Myxovirus Resistance Proteins; D011506:Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016760:Proto-Oncogene Proteins c-fos; C499308:Rag2 protein, mouse; D011947:Receptors, Antigen, B-Cell; D011993:Recombinant Fusion Proteins; D012795:Sialoglycoproteins; C497863:Spn protein, mouse; C064655:V(D)J recombination activating protein 2; D019014:fas Receptor; D019204:GTP-Binding Proteins