UMMS Affiliation

Department of Medicine, Division of Rheumatology

Date

8-1-1989

Document Type

Article

Medical Subject Headings

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

Disciplines

Cell Biology | Cellular and Molecular Physiology | Immunity | Molecular Biology

Abstract

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.

Rights and Permissions

Citation: Mol Cell Biol. 1989 Aug;9(8):3184-92. doi: 10.1128/MCB.9.8.3184. Link to article on publisher's website

Comments

At the time of publication, Ellen Gravallese was not yet affiliated with the University of Massachusetts Medical School.

Publisher PDF posted as allowed by the publisher's author rights policy at http://journals.asm.org/site/misc/ASM_Author_Statement.xhtml.

Related Resources

Link to Article in PubMed

PubMed ID

2477682

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