Interleukin 2- and interleukin 5-induced changes in the binding of regulatory factors to the J-chain gene promoter.
In a primary immune response, B cells require signals from the T-cell lymphokines interleukins 2 and 5 (IL-2 and IL-5) to develop into IgM-secreting cells. One role of IL-2 and IL-5 is to activate transcription of the gene encoding the IgM joining component, the J chain. In this study the activation mechanism was investigated by using an inducible beta-lymphoma cell line to examine J-chain RNA expression and factor binding to the J-chain promoter. The analyses revealed that both IL-2 and IL-5 trigger a decrease in the binding of two promoter-specific nuclear proteins that precedes the appearance of J-chain RNA. In combination the two lymphokines effected nearly additive changes in factor binding and J-chain RNA abundance. Both effects were reversed upon withdrawal of the lymphokine stimulus and both were inhibited in the presence of the T-cell lymphokine IL-4. These findings indicate that the IL-2 and IL-5 signal pathways converge to deliver a common signal that regulates the repressor activities of two lymphokine-responsive promoter elements.
McFadden
H J
HJ
Department of Molecular and Cell Biology, University of California, Berkeley 94720.
Koshland
M E
ME
D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D002467:Cell Nucleus / Q000502:physiology; D005803:Genes, Immunoglobulin; D006801:Humans; D007144:Immunoglobulin J-Chains / Q000235:genetics*; D007075:Immunoglobulin M / Q000235:genetics*; D007376:Interleukin-2 / Q000494:pharmacology*; D015848:Interleukin-5 / Q000494:pharmacology*; D016393:Lymphoma, B-Cell; D051379:Mice; D009687:Nuclear Proteins / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000187:drug effects; D011994:Recombinant Proteins / Q000494:pharmacology; D015183:Restriction Mapping; D016385:TATA Box; D014158:Transcription, Genetic / Q000187:drug effects
D007144:Immunoglobulin J-Chains; D007075:Immunoglobulin M; D007376:Interleukin-2; D015848:Interleukin-5; D009687:Nuclear Proteins; D011994:Recombinant Proteins