Neuronal circuits modulate antigen flow through lymph nodes (IRC11P.420)

Abstract Initial exposure to an antigen, by infection or vaccination, is a critical step in developing protection against subsequent infection. Antigen injected into the dorsum of the mouse hind foot flows to the popliteal lymph node, then to the sciatic lymph node, through the lymphatics and eventually reaching the blood stream. In mice immunized to Keyhole-Limpet Hemocyanin (KLH), flow of IrDye-labeled KLH was restricted through the popliteal and sciatic lymph nodes. Imaging one hour after antigen administration revealed a significant decrease in sciatic and popliteal KLH levels in immunized mice compared to naïve animals (antigen signal in naïve 0.75 ± 0.15 vs sensitized 0.23 ± 0.11, p<0.05). Flow cytometric analysis of lymph node cellular populations revealed that antigen was associated mainly with a CD21+CD23+ mature subset of B-cells (51.9 ± 1.6% of total antigen positive cells)). Blocking neuronal activity with bupivacaine at the lymph nodes of immunized animals resulted in restoration of antigen flow, with an increase in antigen signal (control 0.27 ± 0.016 vs bupivacaine 0.38 ± 0.037, p<0.05). Conversely, direct activation of neuronal signals by noninvasive magnetic stimulation resulted in a significant decrease of antigen trafficking compared to sham controls (sham 1.39 ± 0.18 vs stimulated 0.47 ± 0.11, p<0.001). Taken together, these studies reveal a neuronal circuit that modulates antigen trafficking through a pathway involving a mature subset of B-cells.