1 Institute of Immunology and Immunotherapy, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
2 Department of Rheumatology and Clinical Immunology, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117, Berlin, Germany.
3 Deutsches Rheuma-Forschungszentrum (DRFZ), a Leibniz Institute, Charitéplatz 1, 10117, Berlin, Germany.
4 University of Cambridge Molecular Immunity Unit, MRC Laboratory of Molecular Biology, Cambridge Biomedical Campus, Cambridge, UK.
5 Centre of Membrane Proteins and Receptors (COMPARE), Universities of Birmingham and Nottingham, Birmingham, UK.
6 Institute of Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
7 The Francis Crick Institute, London, UK.
8 Department of Cell Biology, Center for Research and Advanced Studies, The National Polytechnic Institute, Cinvestav-IPN, Av. IPN 2508, San Pedro Zacatenco, Gustavo A. Madero, 07360, Mexico City, Mexico.
9 Thymus Biology Section, Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
10 Division of Experimental Immunology, Institute of Advanced Medical Sciences, University of Tokushima, Tokushima, 770-8503, Japan.
11 Laboratory of Lymphocyte Differentiation, WPI Immunology Frontier Research Center, Osaka University, Osaka, 565-0871, Japan.
12 Laboratory of Lymphocyte Differentiation, RIKEN Center for Integrative Medical Sciences (IMS), Yokohama, Kanagawa, 230-0045, Japan.
13 Imperial College, London, W12 0NN, UK.
14 Centre for Microvascular Research, The William Harvey Research Institute, Queen Mary University London, EC1M 6BQ, London, UK.
15 Centre for Inflammation and Therapeutic Innovation, Queen Mary University London, EC1M 6BQ, London, UK.
16 Institute for Cardiovascular Prevention, Ludwig-Maximilians University, 80336, Munich, Germany.
17 Institute of Immunology and Immunotherapy, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK. firstname.lastname@example.org.
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.