PROLONGED ANTIGEN HALF-LIFE IN THE LYMPHOID FOLLICLES OF SPECIFICALLY IMMUNIZED MICE

Abstract

The kinetics of clearance of 125I from the popliteal lymph nodes and feet of human serum albumin (HSA)-immunized mice was studied following the injection of [125I]-HSA into the hind footpads. Antigen was cleared from both locations rapidly for the first few days. The antigen half-life (T1/2) during this period was a matter of hours. By the end of the 1st wk, the rate of clearance in both sites had changed markedly. The antigen T1/2 in the node between the 1st-6th wk was 8.1 wk (95% confidence interval between 5.1-20 wk) and the antigen T1/2 in the foot was 6.1 wk (95% confidence interval between 3.7-16.6 wk). There was about 20 times more radioactivity in the feet than in the popliteal nodes. Autoradiography of popliteal lymph nodes revealed that antigen was trapped in the medulla., subcapsular sinus, superficial cortex and around lymphoid follicles. During the first few days antigen was cleared from all sites except the follicles. The radioactivity initially trapped in the medulla, subcapsular sinus and superficial cortex was associated with macrophages. Studies with peritoneal macrophages indicated an antigen T1/2 in these cells of 2 h (95% confidence interval between 1.5-3 h). The initial rapid clearance of antigen trapped and catabolized by macrophages and the long-term retention of antigen in the follicles was attributable to trapping and retention by follicular dendritic cells. The large pool of antigen trapped in the foot did not appear to serve as a depot to replace antigen degraded in the node, since amputation of the foot did not alter the level of antigen retained in the node. The long antigen T1/2 in the lymph node follicles indicated that antigen was available in the lymph node and played a role in the maintenance and regulation of immune responses for many months or even years.