High-affinity receptors for interleukin-2 are not required for the induction of human unstimulated B lymphocyte differentiation by this lymphokine.
We have reported that one of the currently known receptors for interleukin-2 (IL-2), the p70 protein, is constitutively expressed on resting T lymphocyte membrane. We demonstrated that exposure of these cells to high concentrations of IL-2 resulted in the transcription of genes whose expression occurred early during cell activation such as cmyc, cmyb protooncogenes, and the Tac gene itself. IL-2 is thought to exert its biological effects by binding to its high-affinity receptors on cell membrane. Recent studies using B cell lines emphasized that within the high-affinity receptor complexes, p55 serves to allow high-affinity binding, and p70, to transduce signals. In this study, we prepared human unstimulated B cells devoid of detectable Tac antigen, and consequently, of the high-affinity receptor complexes. We designed experiments such that no in vitro de novo expressed receptors, if any, could interact with IL-2, so that any biologic events triggered by IL-2 must have been mediated in the absence of the high-affinity receptors. Under these conditions, we demonstrated that a short and unique exposure (1 hr) of these cells to high concentrations (5 nM) of IL-2 allowed its binding to cell membrane and resulted in a competent signal leading to the generation of a majority of 25S Tac mRNA, and a progression signal allowing B cell terminal differentiation into plasma cells.
Bich-Thuy
L T
LT
Laboratory of Molecular Immunology, Ecole Normale Superieure de Lyon, France.
D001402:B-Lymphocytes / Q000166:cytology*; D015152:Blotting, Northern; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression; D006801:Humans; D007147:Immunoglobulin Light Chains / Q000096:biosynthesis; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000494:pharmacology*; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016271:Proto-Oncogene Proteins c-myc; D015375:Receptors, Interleukin-2 / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic
D007147:Immunoglobulin Light Chains; D007376:Interleukin-2; D011518:Proto-Oncogene Proteins; D016271:Proto-Oncogene Proteins c-myc; D015375:Receptors, Interleukin-2