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Recycling of Memory B Cells Between Germinal Center and Lymph Node Subcapsular Sinus Supports Affinity Maturation to Antigenic Drift

Abstract

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) and find that many B cells migrate into the lymph node subcapsular sinus (SCS) guided by sphingosine-1-phosphate (S1P). From the SCS, B cells may exit the lymph node to enter distant tissues, while some B 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 cells and results in less efficient adaption to antigenic variation. Our findings thus suggest that the recycling of antigen variant-specific B cells and transport of antigen back to GC may support affinity maturation to antigenic drift.

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