Studies on the mode of action of the heterologous immunogenicity of a methanol-insoluble fraction of attenuated tubercle bacilli (BCG).

Pre-treatment of mice with a methanol-insoluble residue (MER) of phenol-killed BCG tubercle bacilli affected markedly their immunological response to subsequent immunization with sheep red blood cells (SRBC) and allogeneic red blood cells (ARBC), and their ability to clear intravenously injected colloidal carbon from the circulation. Young adult BALB/c and Swiss albino mice immunized with SRBC usually responded to one or two pre-injections of 0.5 mg each of MER with considerable increments in the total and relative numbers of specifically reactive cells (Jerne plaque-forming cells, PFC) in the spleen. When, however, Swiss albino mice were given MER at ages of 10 weeks or younger and shortly before specific immunization, the splenic content of PFC was depressed. Single preinjection of 0.25–1.0 mg MER stimulated the circulating haemagglutinin response of young adults of the C3H genotype to immunization with Strain A red cells. The heightened responsiveness of MER-stimulated animals was already evident 1–3 days after red cell immunization, and was seen even when intervals of several weeks or months elapsed between MER treatment and immunization. It was also manifest when there was no increase in the total weight or nucleated cell content of the spleen. MER enhanced considerably total and functional carbon clearing activity as early as 2 hours after treatment, prior to any change in the ratio of spleen and liver weights to body weight. These findings point to MER as an active stimulator of antibody formation and phagocytosis in mice, and especially of the early response to antigens and particulate foreign substances.