Kinetics of the Antibody Response to Type III Pneumococcal Polysaccharide

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Abstract
For the first 126 hr after immunization of mice with an optimally immunogenic dose (0.5 µg) of Type III pneumococcal polysaccharide (SSS-III), splenic antibody-forming PFC and serum antibody levels were measured at 2- and 8-hr intervals, respectively. PFC were detected at 28 hr after immunization and then increased through 86 hr after immunization; thereafter, the number of PFC remained nearly constant for the next 20 to 24 hr, and then began to decline. By contrast, serum antibody was first detected 60 hr after immunization. The accumulation of serum antibody continued to lag behined the increase in numbers of PFC by 16 to 20 hr until maximal serum antibody levels were attained; curves fitted to the values obtained for each parameter were nearly parallel. Further analysis of the data indicated that 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 to 24 hr 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. By contrast, when PFC were measured in ALS-treated mice at 2-hr intervals after immunization, PFC were found to increase in a stepwise fashion; however, damping of the size of the stepwise increases did not occur and four additional rounds of recruitment and proliferation were observed after the first 86 hr 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 cells began 24 hr after immunization, increased progressively with time, and functioned to decrease the birth rate of PFC. This suggested the hypothesis that the negative effect of suppressor T cells was directed primarily toward B cell precursors of PFC, diminishing recruitment of PFC from this pool of cells by either halting proliferation of the precursor cells or preventing their differentiation into PFC.

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