2022年新着論文 16　免疫系発生学分野から論文が発表されました

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

Nat Commun. 2022 May 5;13(1):2460. doi: 10.1038/s41467-022-29978-y.

Authors

Yang Zhang^#¹, Laura Garcia-Ibanez^#¹, Carolin Ulbricht^2 3, Laurence S C Lok⁴, Jeremy A Pike^5 6, Jennifer Mueller-Winkler⁷, Thomas W Dennison⁴, John R Ferdinand⁴, Cameron J M Burnett¹, Juan C Yam-Puc¹, Lingling Zhang^1 7, Raul Maqueda Alfaro^1 8, Yousuke Takahama⁹, Izumi Ohigashi¹⁰, Geoffrey Brown⁸, Tomohiro Kurosaki^11 12, Victor L J Tybulewicz^7 13, Antal Rot^{14 15 16}, Anja E Hauser^2 3, Menna R Clatworthy⁴, Kai-Michael Toellner¹⁷

Affiliations

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. k.m.toellner@bham.ac.uk.

^# Contributed equally.

Free PMC article

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

Conflict of interest statement

The authors declare no competing interests.

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