Interleukin 4 induces changes in the chromatin structure of the gamma 1 switch region in resting B cells before switch recombination.
Interleukin 4 (IL-4) can induce the expression of IgG1 in sIgG- murine B cells stimulated with mitogens or through a cognate interaction with T helper (Th) cells. We have investigated the molecular basis for the IL-4-induced switch to IgG1 in lipopolysaccharide (LPS)-stimulated murine B cells and have previously shown that IL-4 induces transcription of the gamma 1 switch region before switch recombination. We now demonstrate that IL-4 induces a DNase I hypersensitive site at the 5' end of the gamma 1 switch region in resting B cells. LPS is not required, but it enhances induction. Hence, the interaction of IL-4 with its receptor results in increased accessibility of the gamma 1 switch region. The more open chromatin structure and increased transcriptional activity may be important in the selection of this region for switch recombination.
Berton
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MT
Department of Microbiology, University of Texas Southwestern Medical Center, Dallas 75235.
Vitetta
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ES
D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000648:ultrastructure*; D015139:Blotting, Southern; D002478:Cells, Cultured; D002843:Chromatin / Q000187:drug effects / Q000648:ultrastructure*; D003850:Deoxyribonuclease I / Q000378:metabolism; D005260:Female; D015322:Gene Rearrangement, B-Lymphocyte; D007134:Immunoglobulin Switch Region / Q000187:drug effects / Q000235:genetics*; D015847:Interleukin-4 / Q000502:physiology*; D008070:Lipopolysaccharides; D051379:Mice; D008807:Mice, Inbred BALB C; D014158:Transcription, Genetic / Q000187:drug effects
D002843:Chromatin; D008070:Lipopolysaccharides; D015847:Interleukin-4; D003850:Deoxyribonuclease I