New synthetic analogs of lipid A as lipopolysaccharide agonists or antagonists of B lymphocyte activation.
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.
Pedron
T
T
Unité d'Immunophysiologie Moléculaire, URA-359 du CNRS, Institut Pasteur, Paris, France.
Girard
R
R
Eustache
J
J
Bulusu
A R
AR
Macher
I
I
Radzyner-Vyplel
H
H
Stütz
P L
PL
Chaby
R
R
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
D008050:Lipid A; D008070:Lipopolysaccharides