Nanoparticle Size Influences Antigen Retention and Presentation in Lymph Node Follicles for Humoral Immunity.
Lymph node follicles capture and retain antigens to induce germinal centers and long-lived humoral immunity. However, control over antigen retention has been limited. Here we discovered that antigen conjugated to nanoparticle carriers of different sizes impacts the intralymph node transport and specific cell interaction. We found that follicular dendritic cell (FDC) networks determine the intralymph node follicle fate of these nanoparticles by clearing smaller ones (5-15 nm) within 48 h and retaining larger ones (50-100 nm) for over 5 weeks. The 50-100 nm-sized nanoparticles had 175-fold more delivery of antigen at the FDC dendrites, 5-fold enhanced humoral immune responses of germinal center B cell formation, and 5-fold more antigen-specific antibody production over 5-15 nm nanoparticles. Our results show that we can tune humoral immunity by simply manipulating the carrier size design to produce effectiveness of vaccines.
['Zhang|Yi-Nan|YN|', 'Lazarovits|James|J|', 'Poon|Wilson|W|', 'Ouyang|Ben|B|', 'Nguyen|Luan N M|LNM|', 'Kingston|Benjamin R|BR|', 'Chan|Warren C W|WCW|0000-0001-5435-4785']
D000818:Animals D000941:Antigens D001402:B-Lymphocytes D003713:Dendritic Cells D018858:Germinal Center D006046:Gold D055767:Immobilized Proteins D056724:Immunity, Humoral D008198:Lymph Nodes D051379:Mice D008810:Mice, Inbred C57BL D058726:Nanoconjugates D010047:Ovalbumin D010316:Particle Size D014612:Vaccines
Nanoparticle antigen retention and presentation lymph node germinal centers follicular dendritic cells complement