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

Zhang, Yang; Garcia-Ibanez, Laura; Ulbricht, Carolin; Lok, Laurence S C; Pike, Jeremy A; Mueller-Winkler, Jennifer; Dennison, Thomas W; Ferdinand, John R et al. · Nat Commun · 2022

basic_science · Level V

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

Medical subject headings