Recycling of memory B cells between germinal center and lymph node subcapsular sinus supports affinity maturation to antigenic drift

Infection or vaccination leads to the development of germinal centers (GC) where B cells evolve high affinity antigen receptors, eventually producing antibody-forming plasma cells or memory B cells. Here we follow the migratory pathways of B cells emerging from germinal centers (B(EM)) and find that many B(EM) cells migrate into the lymph node subcapsular sinus (SCS) guided by sphingosine-1-phosphate (S1P). From the SCS, B(EM) cells may exit the lymph node to enter distant tissues, while some B(EM) cells interact with and take up antigen from SCS macrophages, followed by CCL21-guided return towards the GC. Disruption of local CCL21 gradients inhibits the recycling of B(EM) cells and results in less efficient adaption to antigenic variation. Our findings thus suggest that the recycling of antigen variant-specific B(EM) cells and transport of antigen back to GC may support affinity maturation to antigenic drift.