Regulation of the murine Fc epsilon RII (CD23) gene. Functional characterization of an IL-4 enhancer element.
The murine B cell IgE receptor (Fc epsilon RII, CD23) has been implicated in various functions including IgE regulation, Ag presentation, and B cell differentiation/activation. We have undertaken a series of studies to identify promoter sequences that are important for the constitutive and IL-4-induced expression of the murine Fc epsilon RII in M12.4.5 B lymphoma cells. By use of RNase protection analysis it was established that murine splenic B cells and M12.4.5 cells predominantly express the Fc epsilon RIIa form and that this receptor subtype accounts for the vast majority of IL-4-induced Fc epsilon RII mRNA in B cells. A 101-bp segment of the murine Fc epsilon RII proximal promoter coupled to a heterologous SV40 promoter was found to impart IL-4 inducibility in reporter assays. Removal of either 10 bp from the 5' end or 17 bp from the 3' end of this 101-bp fragment substantially reduced the IL-4 response. Both of these terminal deletions removed sequences that share homology with established IL-4 response elements of MHC class II and Ig (gamma 1 and epsilon) heavy chain genes. In addition, near the center of this 101-bp fragment lies a sequence that is highly homologous with NF-kappa B/LPS response elements previously identified upstream of the A alpha gene. DNA fragments containing this sequence together with one of the putative IL-4 response elements were able to impart a small LPS/IL-4 response in M12.4.5 cells. These results suggest that IL-4 and LPS induction of murine B cell Fc epsilon RII expression is mediated by a complex of transcription factors.
Richards
M L
ML
Division of Immunology, Medical Biology Institute, La Jolla, CA 92037.
Katz
D H
DH
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D004252:DNA Mutational Analysis; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation; D006801:Humans; D015847:Interleukin-4 / Q000502:physiology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D017455:Receptors, IgE / Q000235:genetics*; D016415:Sequence Alignment; D017384:Sequence Deletion; D012689:Sequence Homology, Nucleic Acid; D014158:Transcription, Genetic
D008070:Lipopolysaccharides; D012333:RNA, Messenger; D017455:Receptors, IgE; D015847:Interleukin-4