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

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journal contribution
posted on 13.05.2022, 10:35 by Yang Zhang, Laura Garcia-Ibanez, Carolin Ulbricht, Laurence SC Lok, Jeremy A Pike, Jennifer Mueller-Winkler, Thomas W Dennison, John R Ferdinand, Cameron JM Burnett, Juan C Yam-Puc, Lingling Zhang, Raul Maqueda Alfaro, Yousuke Takahama, Izumi Ohigashi, Geoffrey Brown, Tomohiro Kurosaki, Victor LJ Tybulewicz, Antal Rot, Anja E Hauser, Menna R Clatworthy, Kai-Michael Toellner
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 (BEM) and find that many BEM cells migrate into the lymph node subcapsular sinus (SCS) guided by sphingosine-1-phosphate (S1P). From the SCS, BEM cells may exit the lymph node to enter distant tissues, while some BEM 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 BEM cells and results in less efficient adaption to antigenic variation. Our findings thus suggest that the recycling of antigen variant-specific BEM cells and transport of antigen back to GC may support affinity maturation to antigenic drift.

Funding

Crick (Grant ID: 10194, Grant title: Tybulewicz FC001194)

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