Modulation of the immune response by a methanol-insoluble fraction of attenuated tubercle bacilli (BCG). II. Relationship of antigen dose to heightened primary and secondary immune responses to sheep red blood cells.

A methanol extraction residue (MER) of BCG has previously been shown to heighten host resistance to a subsequent challenge with microorganisms or syngeneic tumour grafts and to stimulate the antibody response to sheep red blood cells (SRBC) and phage T. Present investigations on the effect of antigen dose on MER stimulation of the primary and secondary response to SRBC indicated that: (1) Pretreatment by MER stimulates the early primary response most effectively when the immunizing dose of SRBC is less than maximum, and this is due to a greater increase by MER of 19S antibody with low doses of antigen than with high doses of SRBC. Maximum 7S antibody production is higher in MER treated animals at all antigen doses. (2) MER administered after low doses of SRBC but not high doses stimulates the ongoing primary haemagglutinin response. (3) Maximum secondary responses of mice treated with MER before priming are considerably elevated above the corresponding controls and the secondary responses in treated mice are not inhibited by high priming doses of antigen. These results are discussed in relation to the locus of MER activity.