Rats receiving a single antigen injection on the day of birth or at age 7 days had no measurable response to the antigen. Rats receiving a single antigen injection at age 17 days and sacrificed 4 days later had an unequivocal response to the antigen. The spleens had about one-tenth as many plaque-forming cells as spleens of adult animals immunized similarly, but the antibody titers were as high as titers for adult animals. Presumably the high titers of these young animals resulted from the high ratio of plaque-forming cells to body weight and blood volume. Adult animals receiving a single antigen injection had a peak or near peak plaque-forming cell response 4 days after immunization; at this time, sera contained high titers of 19S antibody and the numbers of plaque-forming cells in spleens correlated reasonably well with circulating antibody titers. 7S antibody appeared in serum 5 or 6 days after immunization. The numbers of plaque-forming cells declined progressively 2 and 3 weeks after immunization.

Repeated twice weekly, injections of the antigen in adult rats produced a marked decline and then stabilization of numbers of plaque-forming cells in spleens. Although the numbers of plaque-forming cells were fewer, titers of 19S and 7S antibody stabilized at high levels. A progressive recovery of the plaque-forming cell response and a rise in antibody titer occurred when the interval between the last 2 injections was increased from 3 to 10, 17, or 32 days. These findings suggested that repeated closely spaced antigen injections interfered with either cell division or maturation of antibody-forming cells. As the interval between injections was increased, additional antibody-forming cells matured or were formed through cell division. Thus, relatively constant antigenic stimulation provided a mechanism for controlling or limiting the response of antibody-forming cells.

In the following paper, it will be shown that this mechanism operating together with a homeostatic mechanism which prevents induction of new antibody-forming cells serves to regulate the immune response to repeated injections of antigen.