Memory-like B cells emerging from germinal centres recycle through the subcapsular sinus

Infection or vaccination leads to the development of germinal centers (GCs) where B cells evolve high affinity antigen receptors, eventually producing antibody-forming plasma cells or memory B cells. We followed the migratory pathways of B cells emerging from germinal centers (BEM) and found that many migrated into the lymph node subcapsular sinus (SCS) guided by sphingosine-1-phosphate (S1P). From there, B cells may exit the lymph node to enter distant tissues. Some BEM cells interacted with and took up antigen from SCS macrophages, followed by CCL21-guided return towards the GC. Disruption of local CCL21 gradients inhibited the recycling of BEM cells and resulted in less efficient adaption to antigenic variation. Our findings suggest that the recycling of BEM cells, that transport antigen and that contain the genetic code for B cell receptor variants, may support affinity maturation to antigenic drift. ### Competing Interest Statement The authors have declared no competing interest. * BEM : memory like B cell emerging from germinal centers BCM : circulating memory B cell S1P : sphingosine-1-phosphate GC : germinal center ACKR4 : atypical chemokine receptor 4 NP-CGG : 4-hydroxy-nitrophenyl coupled to chicken gamma globulin QM : quasi-monoclonal mouse SCS : subcapsular sinus pLN : popliteal lymph node drLN : draining lymph node distLN : distant lymph node DC : dendritic cell FDC : Follicular dendritic cells IC : immune complex