KINETICS OF ANTIBODY-RESPONSE TO TYPE-3 PNEUMOCOCCAL POLYSACCHARIDE .3. EVIDENCE THAT SUPPRESSOR CELLS FUNCTION BY INHIBITING RECRUITMENT AND PROLIFERATION OF ANTIBODY-PRODUCING CELLS

Abstract

For the first 126 h after immunization of mice with an optimally immunogenic dose (0.5 .mu.g) of Type III pneumococcal polysaccharide, splenic antibody-forming PFC [plaque-forming cells] and serum antibody levels were measured at 2- and 8-h intervals, respectively. PFC were detected at 28 h after immunization and then increased through 86 h after immunization; thereafter, the number of PFC remained nearly constant for the next 20-24 h, then began to decline. Serum antibody was first detected 60 h after immunization. The accumulation of serum antibody continued to lag behind the increase in numbers of PFC by 16-20 h until maximal serum antibody levels were attained; curves fitted to the values obtained for each parameter were nearly parallel. PFC increased in a stepwise fashion, producing a staircase pattern that would be expected for a synchronous proliferation of PFC with multiple recruitment events. Experiments in which mice were injected with a mitotic inhibitor at time intervals after immunization indicated that those precursor cells, capable of differentiating into PFC, were proliferating already by 12-24 h after immunization. The size of the stepwise increases in the number of PFC decreased with time after immunization, indicating that recruitment from this pool of precursor cells decreased with time. When PFC were measured in [horse] anti-lymphocyte serum treated mice at 2-hr intervals after immunization PFC increased in a stepwise fashion; damping of the size of the stepwise increases did not occur, and 4 additional rounds of recruitment and proliferation were observed after the first 86 h after immunization. These findings allowed construction of a mathematical model to describe the effect of suppressor cells on the PFC response to an optimally immunogenic dose of antigen. In this model, the negative effect of suppressor T [thymus-derived] cells began 24 h after immunozation, increased progressively with time, and functioned to decrease the birth rate of PFC. The negative effect of suppressor T cells was probably directed primarily toward bone marrow-derived cell precursors of PFC, diminishing recruitment of PFC from this pool of cells by halting proliferation of the precursor cells or preventing their differentiation into PFC.