In vivo activation of mouse spleen lymphocytes by lipid A in carrier-free form.

The immunogenic potential of lipid A, isolated from Salmonella minnesota R595 and made soluble by mild alkaline hydrolysis, was investigated using ICR mice and a modification of the Jerne plaque assay. In the absence of carrier protein of Freund's adjuvant, a single intravenous injection of 100 microgram lipid A induced the development of anti-lipid A antibody-producing cells in the spleen. At the doses used, no heterophile-antibody plaques specific for sheep red blood cell antigen were detectable in recipients of alkali-treated lipid A. Moreover, the specific (anti-lipid A) plaque-forming ability of mice injected with alkali-treated lipid A. Moreover, the specific (anti-lipid A) plaque-forming ability of mice injected with alkali-treated lipid A nearly equalled the ability of mice injected with free lipid A, suggesting that mild alkaline hydrolysis treatment left intact the immunodominance of free lipid A. We also found that alkali-treated lipid A induced an increase in [3H]-thymidine incorporation by splenic T and B lymphocytes. This suggests the possible collaboration of T and B cells in the in vivo production of anti-lipid A antibody.