IFN-gamma induces the kappa intron enhancer via an IFN-stimulated response element.
IFN-gamma is a potent inducer of Ig kappa light chain gene transcription in 70Z/3 pre-B cells, but the mechanism of this induction has not been elucidated. The kappa intron enhancer contains a sequence closely resembling the IFN-stimulated response element (ISRE). We have determined that the kappa intron enhancer is IFN-gamma inducible in 70Z/3 cells and that the ISRE is required for this induction. The kappa intron ISRE specifically bound IFN response factor-1 (IRF-1) and the constitutively expressed IRF-2. This ISRE is a multifunctional motif that also binds the LPS-inducible factor kappaBF-A and is located within the kappaBS region, which confers B cell specific activity to this enhancer. However, since the expression of IRF-1 is not restricted to B cells, it must not be sufficient for the induction of kappa transcription. Furthermore, in the pre-B cell line 38B9, which is representative of an earlier stage in pre-B cell development than the 70Z/3 cell line, the kappa intron enhancer was not induced by IFN-gamma despite the activation of IRF-1. These findings suggest that IFN-gamma activation of kappa gene transcription during B cell maturation may be developmentally controlled by elements that restrict the activity of the ISRE within the context of the intron enhancer.
Damore
M A
MA
Molecular Biology Insitute, University of California, Los Angeles 90095, USA.
Omori
S A
SA
Wall
R
R
D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology*; D001483:Base Sequence; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism; D004742:Enhancer Elements, Genetic / Q000187:drug effects*; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000276:immunology; D007145:Immunoglobulin kappa-Chains / Q000235:genetics*; D050856:Interferon Regulatory Factor-1; D050836:Interferon Regulatory Factor-2; D007371:Interferon-gamma / Q000494:pharmacology*; D007438:Introns; D051379:Mice; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes / Q000235:genetics; D010750:Phosphoproteins / Q000378:metabolism; D010957:Plasmids / Q000235:genetics; D011994:Recombinant Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D014162:Transfection
D004268:DNA-Binding Proteins; D007145:Immunoglobulin kappa-Chains; D050856:Interferon Regulatory Factor-1; D050836:Interferon Regulatory Factor-2; C494258:Irf1 protein, mouse; C494230:Irf2 protein, mouse; D015345:Oligonucleotide Probes; D010750:Phosphoproteins; D011994:Recombinant Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D007371:Interferon-gamma