Abstract
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.
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, CD*
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Apoptosis / drug effects
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Apoptosis / genetics*
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B-Lymphocytes / cytology*
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B-Lymphocytes / drug effects
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Bone Marrow Cells
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Cell Differentiation / drug effects
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Cell Line
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Coculture Techniques
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Connective Tissue / physiology
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DNA-Binding Proteins*
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GTP-Binding Proteins*
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Gene Expression Regulation / drug effects
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Genes, fos*
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H-2 Antigens / immunology
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Hematopoietic Stem Cells / cytology*
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Hematopoietic Stem Cells / drug effects
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Hematopoietic Stem Cells / immunology
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Interferon-alpha / pharmacology
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Interleukin-7 / pharmacology
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Leukosialin
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Liver / cytology
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Liver / embryology
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Mice
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Mice, Inbred C3H
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Mice, Inbred C57BL
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Mice, Transgenic
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Myxovirus Resistance Proteins
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Promoter Regions, Genetic / drug effects
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Protein Biosynthesis
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Proteins / genetics
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Proto-Oncogene Proteins c-bcl-2 / biosynthesis
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Proto-Oncogene Proteins c-bcl-2 / genetics
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Proto-Oncogene Proteins c-fos / biosynthesis*
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Receptors, Antigen, B-Cell / immunology*
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Recombinant Fusion Proteins / biosynthesis
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Sialoglycoproteins / analysis*
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fas Receptor / biosynthesis
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fas Receptor / genetics
Substances
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Antigens, CD
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DNA-Binding Proteins
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H-2 Antigens
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H-2K(K) antigen
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H-2Kb protein, mouse
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Interferon-alpha
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Interleukin-7
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Leukosialin
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Mx1 protein, mouse
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Myxovirus Resistance Proteins
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Proteins
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Proto-Oncogene Proteins c-bcl-2
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Proto-Oncogene Proteins c-fos
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Rag2 protein, mouse
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Receptors, Antigen, B-Cell
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Recombinant Fusion Proteins
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Sialoglycoproteins
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Spn protein, mouse
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V(D)J recombination activating protein 2
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fas Receptor
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GTP-Binding Proteins