Dynamic Aspects of the Formation of Serum Antibody in Rabbits

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Abstract
Summary: By use of a soluble protein antigen which is rapidly eliminated from the circulation and a sensitive photometric passive hemagglutination titration for antibody, it was possible to observe the increase of serum titer against bovine serum globulin over a 104- to 105-fold range. The early rise in titer followed an exponential progression with doubling times of 2.2 to 3.7 hr. This was usually followed by a second phase with a doubling time of 3.6 to 6.2 hr. Either time is appreciably shorter than the generation times which have been reported for mammalian cells. Following the early exponential phase, most of the antibody was synthesized at or close to the maximal absolute rate attained, giving an arithmetic increase in titer. This arithmetic phase was analyzed mathematically to show that the experimental curves could be accounted for as the difference between a constant rate of formation and exponential decay. The rate of formation of antibody fell to a very low level within 12 hr of peak titer. In four of the six rabbits about one-fourth of the antibody at peak titer had a half-life much shorter than those previously reported for rabbit anti-protein antibodies. Published data for serum antibody during the reinjection response to a variety of antigens is reviewed. It is suggested that an early exponential rise of titer followed by production of most of the antibody at a constant rate may be characteristic for the secondary serum antibody response in rabbits after a single intravenous reinjection of many antigens that are rapidly cleared from the circulation. Furthermore, such a sequence of exponential and arithmetic phases is consistent with what is known of the cellular response in lympoid tissues following antigenic stimulation.

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