Synthesis of germ-line gamma 1 immunoglobulin heavy-chain transcripts in resting B cells: induction by interleukin 4 and inhibition by interferon gamma.
Interleukin 4 (IL-4) induces the expression of IgG1 and IgE in lipopolysaccharide-stimulated B cells. Previous studies have suggested that heavy-chain class switching may be regulated by increasing the accessibility of specific switch regions to switch recombinases. In this study, we have used an RNase protection assay to demonstrate that IL-4 induces expression of germ-line gamma 1 transcripts in B cells within 4 hr of culture; induction is dose-dependent and is inhibited by interferon gamma. IL-4 alone is capable of inducing the expression of germ-line gamma 1 transcripts in small, resting B cells, but lipopolysaccharide enhances expression. The germ-line transcripts are the same size (1.8 and 3.4 kilobases) as the secreted and membrane forms of the functional gamma 1 mRNAs and presumably result from the splicing of an upstream switch-region exon(s) to the gamma 1 constant-region exon(s). These data strongly support the "accessibility" model for the regulation of isotype switching and suggest that lymphokines such as IL-4 may direct specific switch events by transcriptional activation of the corresponding switch regions.
Berton
M T
MT
Department of Microbiology, University of Texas Southwestern Medical Center, Dallas 75235.
Uhr
J W
JW
Vitetta
E S
ES
D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology*; D015152:Blotting, Northern; D005786:Gene Expression Regulation / Q000187:drug effects; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007142:Immunoglobulin gamma-Chains / Q000235:genetics*; D007371:Interferon-gamma / Q000494:pharmacology*; D015847:Interleukin-4; D007378:Interleukins / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000235:genetics; D011995:Recombination, Genetic; D014158:Transcription, Genetic / Q000187:drug effects
D007143:Immunoglobulin Heavy Chains; D007142:Immunoglobulin gamma-Chains; D007378:Interleukins; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D015847:Interleukin-4; D007371:Interferon-gamma