title: New synthetic analogs of lipid A as lipopolysaccharide agonists or antagonists of B lymphocyte activation.
abstract: We have studied the ability of synthetic analogs of lipid A to mimic lipopolysaccharide (LPS) for activation of 70Z/3 pre-B cells (expression of surface Igs) or to antagonize this effect. The results indicate that the presence of glucosamine (mono- or disaccharide) as a 'backbone' for the attachment of fatty acids is not necessary for activation of cells of the B lineage. Phosphate groups are not necessary either. Other structural features such as the configuration of particular asymmetric carbons, and the distance between an anionic group and an N-acyl chain, seem to be much more critical parameters for activation of B cells. Among the synthetic lipids which were unable to activate 70Z/3 cells, one compound, consisting of N,N-acylated and bisphosphorylated 2,3-dideoxy-2,3-diamino-D-glucose, behaved as a specific LPS antagonist and blocked also the activation triggered by the other synthetic inducers. The influence of the synthetic lipids on the entry of mature mouse B lymphocytes into the G1A phase of the cell cycle (cell enlargement) was also investigated. A high correlation was observed between the potency to activate pre-B cells and the ability to induce blast formation in mature B cells.
authors.affiliation: Unité d'Immunophysiologie Moléculaire, URA-359 du CNRS, Institut Pasteur, Paris, France.
authors.forename: T
authors.initials: T
authors.lastname: Pedron
authors.forename: R
authors.initials: R
authors.lastname: Girard
authors.forename: J
authors.initials: J
authors.lastname: Eustache
authors.forename: A R
authors.initials: AR
authors.lastname: Bulusu
authors.forename: I
authors.initials: I
authors.lastname: Macher
authors.forename: H
authors.initials: H
authors.lastname: Radzyner-Vyplel
authors.forename: P L
authors.initials: PL
authors.lastname: Stütz
authors.forename: R
authors.initials: R
authors.lastname: Chaby
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002454:Cell Differentiation; D005260:Female; D066298:In Vitro Techniques; D008050:Lipid A / Q000031:analogs & derivatives* / Q000737:chemistry / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008809:Mice, Inbred C3H; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D008050:Lipid A; D008070:Lipopolysaccharides