Lipid A-dependent Lymphocyte Proliferation in "endotoxin-nonresponder" Mice

Lipopolysaccharides (LPS) with a subunit composition reduced in heterogeneity were prepared by gel-filtration chromatography of detergent-dissociated LPS from the smooth strain of Escherichia coli 055:B5. The splenocyte mitogenic activity of reassociated column-fraction pools was markedly dependent on the ratio of O-antigen polysaccharide to lipid A, where the activity of the fraction richest in lipid A (F5 LPS) was approximately three orders of magnitude greater than the least active fraction (F1 LPS). The F5 LPS, which contains only a trace of O-antigen polysaccharide, induces a spleen-cell proliferative response in C3H/HeJ "LPS nonresponder" spleen cells. This mitogenic activity is not present in either unfractionated LPS or the other column fractions. These latter findings indicate that LPS macromolecular aggregates of the appropriate physico-chemical structure and/or compositions have the capacity to elicit C3H/HeJ spleen-cell proliferative responses.