Surface Ig receptor-induced nuclear AP-1-dependent gene expression in B lymphocytes.
The relationship between signals generated via the sIgR complex of B lymphocytes and subsequent changes in gene expression is poorly understood at the molecular level. To illuminate mechanisms that may couple these events, we examined the expression and function of tetradecanoyl phorbol acetate-response element (TRE)-binding proteins (i.e., activator protein 1, (AP-1)) in the murine B lymphoma cell line BAL-17.7.1 (BAL-17), which models primary B lymphocyte responses in a number of respects. Cross-linking of sIgR led to substantial induction of nuclear AP-1, in BAL-17 B cells, that bound the TRE, as detected by electrophoretic mobility shift assay. The sIgR-induced TRE-binding activity consisted of both Jun and Fos proteins, on the basis of immunoreactivity of nucleoprotein complexes with specific antisera. In addition, immunoprecipitation with specific antisera showed that de novo synthesis of Jun-B and c-Jun proteins, accompanied by c-Fos, was stimulated after cross-linking of sIgR on BAL-17 B cells. Transient transfection of BAL-17 B cells with reporter gene constructs showed that B cell AP-1 failed to trans-activate the TRE-containing human collagenase gene promoter, for which activity is dependent upon functional expression of cellular c-Jun. In contrast, sIg-induced AP-1 trans-activated a HSV-tk promoter that contained three TRE; this pattern of gene expression is consistent with the presence of functional Jun-B-containing AP-1 in B lymphocytes. These results are the first to attribute a functional role to sIgR-mediated AP-1 in B lymphoid cells and suggest that AP-1 functions to couple the sIgR complex to changes in nuclear gene expression.
Chiles
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Department of Medicine, Evans Memorial Department of Clinical Research, Boston University Medical Center, MA 02118.
Rothstein
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D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D015870:Gene Expression; D066298:In Vitro Techniques; D051379:Mice; D011401:Promoter Regions, Genetic; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D011947:Receptors, Antigen, B-Cell / Q000502:physiology*; D012045:Regulatory Sequences, Nucleic Acid; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D011947:Receptors, Antigen, B-Cell