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.