Department of Medicine, Division of Rheumatology
Animals; B-Lymphocytes; Base Sequence; Cell Nucleus; DNA; DNA-Binding Proteins; Deoxyribonuclease I; Histocompatibility Antigens Class II; Lipopolysaccharides; Mice; Mice, Nude; Molecular Sequence Data; NF-kappa B; RNA; Spleen; Transcription Factors
Cell Biology | Cellular and Molecular Physiology | Immunity | Molecular Biology
Class II (Ia) major histocompatibility complex molecules are cell surface proteins normally expressed by a limited subset of cells of the immune system. These molecules regulate the activation of T cells and are required for the presentation of antigens and the initiation of immune responses. The expression of Ia in B cells is determined by both the developmental stage of the B cell and by certain external stimuli. It has been demonstrated previously that treatment of B cells with lipopolysaccharide (LPS) results in increased surface expression of Ia protein. However, we have confirmed that LPS treatment results in a significant decrease in mRNA encoding the Ia proteins which persists for at least 18 h. Within the upstream regulatory region of A alpha k, an NF-kappa B-like binding site is present. We have identified an LPS-induced DNA-binding protein in extracts from athymic mice whose spleens consist predominantly of B cells. Binding activity is present in low levels in unstimulated spleen cells and is increased by LPS treatment. This protein binds to two sites in a regulatory region of the Ia A alpha k gene, one of which contains the NF-kappa B-like binding site. DNA fragments containing these sites cross-compete for protein binding. Analysis by DNase I footprinting identified a target binding sequence, named the LPS-responsive element. Although this target sequence contains an NF-kappa B-like binding site, competition with a mutant oligonucleotide demonstrated that bases critical for NF-kappa B binding are not required for binding of the LPS-inducible protein. Therefore, we hypothesized that this inducible protein represents a new mediator of LPS action, distinct from NF-kappa B, and may be one mechanism to account for the decrease in mRNA encoding the Ia proteins.
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DOI of Published Version
Mol Cell Biol. 1989 Aug;9(8):3184-92. doi: 10.1128/MCB.9.8.3184. Link to article on publisher's website
Molecular and cellular biology
Gravallese, Ellen M.; Boothby, Mark R.; Smas, Cynthia M.; and Glimcher, Laurie H., "A lipopolysaccharide-induced DNA-binding protein for a class II gene in B cells is distinct from NF-kappa B" (1989). Rheumatology Publications and Presentations. 11.