The influence of IL-7 V(D)J recombination.
The influence of interleukin-7 (IL-7) on V(D)J recombination was investigated directly in the V(D)J recombination competent pre-B-cell line 38B9. The addition of IL-7 to the medium reduced the V(D)J recombination rate by 52-64%. This reduction was insensitive to the addition of cyclosporin A, indicating that the repression by IL-7 is not mediated by phosphatase 2B. The repression mechanism of IL-7 did not synergize with those of the protein kinase C activator 12-O-Tetradecanoylphorbol-13-acetate (TPA) and the intracellular Ca2+ mobilizer thapsigargin. The actin of IL-7 blocked by the addition of the protein kinase A stimulator caffeine and the synthetic glucocorticoid dexamethasone. IL-7 did not change the m-RNA levels of the V(D)J recombination activating genes RAG-1 and RAG-2, therefore IL-7 must exert its influence on V(D)J recombination either by post-transcriptional regulation of the RAG genes or by the regulation of other genes that are involved in V(D)J recombination. Although IL-7 may be necessary for the induction of and maintenance of V(D)J recombination during some stages of lymphocyte precursor development, it reduces the V(D)J recombination activity in pre-B cells.
Döbbeling
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Department of Dermatology, University Hospital of Zürich, Switzerland.
D000818:Animals; D002460:Cell Line; D016654:Genes, RAG-1; D015851:Interleukin-7 / Q000494:pharmacology*; D051379:Mice; D011947:Receptors, Antigen, B-Cell / Q000235:genetics*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D011995:Recombination, Genetic / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects; D014158:Transcription, Genetic / Q000187:drug effects
D015851:Interleukin-7; D011947:Receptors, Antigen, B-Cell; D011948:Receptors, Antigen, T-Cell