Expression of the immunoglobulin J chain in a murine B lymphoma is driven by autocrine production of interleukin 2.
Expression of the immunoglobulin J chain is initiated by lymphokine signals delivered to activated B cells during a primary immune response. In the mature murine B cell line, CH12.LX, IL-5 and LPS but not IL-2 were found to greatly enhance basal levels of J chain gene expression. Analysis of the IL-2 receptor (IL-2R) showed two defects: an unusually low expression of the IL-2R alpha chain and little or no IL-2R beta chain. Treatment with IL-5 strongly amplified IL-2R alpha chain expression in CH12.LX cells, yet failed to confer IL-2 responsiveness. However, when the IL-2R beta chain was introduced by stable transfection, the cells expressed 400-500 high affinity IL-2R and responded to IL-2 with increased J chain expression. Surprisingly, in the absence of exogenous lymphokine stimulation, the basal levels of J chain and IL-2R alpha in all IL-2R beta transfectants became significantly elevated over time. Analysis showed that CH12.LX cells constitutively synthesized IL-2 and, given a functional IL-2R, responded to the lymphokine in an autocrine fashion to upregulate both J chain and IL-2R alpha. Thus, CH12.LX cells provide a model cell line in which the role of the IL-2R beta chain in differentiative events such as J chain upregulation can be examined.
Department of Molecular and Cell Biology, University of California, Berkeley 94720, USA.
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Gaffen
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Wang
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Koshland
D000818:Animals; D019138:Antibodies, Blocking / Q000276:immunology; D005434:Flow Cytometry; D005803:Genes, Immunoglobulin; D007144:Immunoglobulin J-Chains / Q000235:genetics*; D007376:Interleukin-2 / Q000096:biosynthesis* / Q000276:immunology; D016393:Lymphoma, B-Cell / Q000276:immunology*; D051379:Mice; D016133:Polymerase Chain Reaction; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000276:immunology; D014162:Transfection; D014407:Tumor Cells, Cultured
D019138:Antibodies, Blocking; D007144:Immunoglobulin J-Chains; D007376:Interleukin-2; D011994:Recombinant Proteins