A lipopolysaccharide-induced DNA-binding protein for a class II gene in B cells is distinct from NF-kappa B.

Gravallese EM, Boothby MR, Smas CM, Glimcher LH
Mol Cell Biol. 1989 9 (8): 3184-92

PMID: 2477682 · PMCID: PMC362362 · DOI:10.1128/mcb.9.8.3184

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.

MeSH Terms (16)

Animals B-Lymphocytes Base Sequence Cell Nucleus Deoxyribonuclease I DNA DNA-Binding Proteins Histocompatibility Antigens Class II Lipopolysaccharides Mice Mice, Nude Molecular Sequence Data NF-kappa B RNA Spleen Transcription Factors

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