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. Activated B cell enter germinal centers (GC) to become plasma cells and memory B cells. Here the authors show that some memory B cells recycle to GC via CCL-21 mediated chemotaxis to deliver antigens from the lymph node subcapsular sinus (SCS) to potentially contribute to affinity maturation and antigenic drift.