Formation of lymph follicles in draining lymph nodes after local injection of various antigenic substances in mice.

Formation of lymph follicles in draining popliteal lymph nodes was examined in 8-week-old, male C57Bl/6 mice which had been injected in the rear footpad with any one of eleven test substances including thymus-dependent and thymus-independent antigens, and killed after 6-14 days. HGG (10-100 micrograms), MGG, tetanus and diphtheria toxoids (2-10 Lf) and influenza HA vaccine (35 CCA) induced germinal centers in association with existing follicles, but failed to produce new follicles in draining nodes. KLH (10-100 micrograms), SRBC (1 X 10(8)) and formalin-killed pertussis organisms (5 X 10(8)) induced germinal centers in existing follicles and also produced new follicles which soon developed germinal centers. Levan and PVP (10-100 micrograms) induced neither germinal centers nor new follicles. Ferritin (100 micrograms) virtually failed to induce germinal centers but produced a significant number of new primary follicles. In further experiments, artificially aggregated substances were examined with regards to their ability of inducing lymph follicle formation in draining nodes. Precipitated proteins such as alum-precipitated PHA, HGG, tetanus and diphtheria toxoids, "Sepharose"-PHA and "Sepharose"-HGG induced a significant number of new follicles. These observations suggest that efficient follicle formation is associated with particulate and high-molecular-weight antigens which are liable to be phagocytized, whereas soluble, poorly phagocytized antigens tend to be inefficient. Soluble proteins may be effective if given in precipitated form. Thymic dependency appears to be irrelevant. The present results point to a possible participation of macrophages in the mechanism of follicle formation.