A histological and experimental study on the fate of an increased number of lymph follicles produced in the mouse popliteal lymph node by exogenous antigen stimulation

Eight-week-old female C57B1/6 mice were injected with endotoxin LPS and/or other antigens into the left hind footpad, and then the number of lymph follicles in the draining popliteal lymph nodes was examined. In untreated mice each popliteal node contained 10-12 lymph follicles at both 8 and 15 weeks of age. Animals given 50 micrograms of LPS at 8 weeks of age showed an increase in the number of lymph follicles 3 weeks later, but this number returned to normal levels by 15 weeks after the LPS injection. After a 2-micrograms-LPS injection at 23 weeks of age, the number of lymph follicles in the draining lymph node was unchanged, but that in animals given the 2-micrograms-injection 15 weeks after the 50-micrograms-LPS injection was significantly increased. In animals receiving 2 Lf of diphtheria toxoid, instead of the 2-micrograms-LPS, at 15 weeks after a 50-micrograms-LPS injection, the number of lymph follicles per draining node was within the normal range. In one group of mice, the initial injection of 50-micrograms-LPS at 8 weeks of age was followed by injections every third week of several kinds of antigens which had been shown to be ineffective in inducing follicle formation. Here, the number of lymph follicles in the draining popliteal node was kept to significantly increased levels at 25 weeks of age. The present results suggest that, while most lymph follicles normally developing in the lymph node are maintained for a long time under normal conditions, many lymph follicles induced by antigenic challenge have a limited life span and undergo atrophy unless they are periodically activated by additional antigenic stimuli, and that atrophied follicles finally become unable to respond to antigenic stimulation. It is also suggested that antigenic materials which trigger the formation of lymph follicles in the primary challenge can evoke follicle formation more efficiently in the secondary challenge.