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

Published version
Peer-reviewed

Change log

Authors

Zhang, Yang 
Garcia-Ibanez, Laura 
Pike, Jeremy A 

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 (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.

Description

Keywords

Article, /631/250/2152/2153/1982, /631/250/2152/2153/1571, /631/250/1620/1616, /631/250/2503, /13/31, /13/21, /13/1, /13/51, /14/35, /14/63, /14/69, /38/47, /38/77, /38/88, /64/60, article

Journal Title

Nat Commun

Conference Name

Journal ISSN

2041-1723
2041-1723

Volume Title

13

Publisher

Nature Publishing Group UK
Sponsorship
RCUK | Biotechnology and Biological Sciences Research Council (BBSRC) (BB/S003800/1, BB/S003800/1, BB/M025292/1)
European Commission (EC) (DECIDE, DECIDE)
Wellcome Trust (Wellcome) (104384/Z/14/Z)
Cancer Research UK (CRUK) (FC001194)
Wellcome Trust (Wellcome) (FC001194)
Deutsche Forschungsgemeinschaft (German Research Foundation) (TP17, C01, HA5354/10-1, TRR130)
RCUK | Medical Research Council (MRC) (MR/N024907/1, MR/P001874/1)
DH | National Institute for Health Research (NIHR) (RP-2017-08-ST2-002)