Abstract

Vaccine-induced immunity depends on the generation of memory B cells (MBC). However, where and how MBCs are reactivated to make neutralising antibodies remain unknown. Here we show that MBCs are prepositioned in a subcapsular niche in lymph nodes where, upon reactivation by antigen, they rapidly proliferate and differentiate into antibody-secreting plasma cells in the subcapsular proliferative foci (SPF). This novel structure is enriched for signals provided by T follicular helper cells and antigen-presenting subcapsular sinus macrophages. Compared with contemporaneous secondary germinal centres, SPF have distinct single-cell molecular signature, cell migration pattern and plasma cell output. Moreover, SPF are found both in human and mouse lymph nodes, suggesting that they are conserved throughout mammalian evolution. Our data thus reveal that SPF is a seat of immunological memory that may be exploited to rapidly mobilise secondary antibody responses and improve vaccine efficacy.

Details

Title
Memory B cells are reactivated in subcapsular proliferative foci of lymph nodes
Author
Moran, Imogen 1 ; Nguyen, Akira 1 ; Khoo, Weng Hua 2 ; Butt, Danyal 3 ; Bourne, Katherine 4 ; Young, Clara 4 ; Hermes, Jana R 4 ; Biro, Maté 5   VIAFID ORCID Logo  ; Gracie, Gary 6 ; Ma, Cindy S 1 ; C Mee Ling Munier 7   VIAFID ORCID Logo  ; Luciani, Fabio 8 ; Zaunders, John 9 ; Parker, Andrew 6 ; Kelleher, Anthony D 9 ; Tangye, Stuart G 1   VIAFID ORCID Logo  ; Croucher, Peter I 10 ; Brink, Robert 1 ; Read, Mark N 11 ; Tri Giang Phan 1   VIAFID ORCID Logo 

1  Immunology Division, Garvan Institute of Medical Research, Sydney, NSW, Australia; St Vincent’s Clinical School, Faculty of Medicine, UNSW, Sydney, NSW, Australia 
2  Division of Bone Biology, Garvan Institute of Medical Research, Sydney, NSW, Australia; School of Biotechnology and Biomolecular Sciences, Faculty of Science, UNSW, Sydney, NSW, Australia 
3  Immunology Division, Garvan Institute of Medical Research, Sydney, NSW, Australia; Biologics Research and Development, Teva Pharmaceuticals, Macquarie Park, NSW, Australia 
4  Immunology Division, Garvan Institute of Medical Research, Sydney, NSW, Australia 
5  EMBL Australia, Single Molecule Science Node, School of Medical Sciences, UNSW, Sydney, NSW, Australia 
6  Department of Anatomical Pathology, St Vincent’s Hospital, Sydney, NSW, Australia 
7  The Kirby Institute for Infection and Immunity in Society, UNSW, Sydney, NSW, Australia 
8  The Kirby Institute for Infection and Immunity in Society, UNSW, Sydney, NSW, Australia; School of Medical Sciences, Faculty of Medicine, UNSW, Sydney, NSW, Australia 
9  The Kirby Institute for Infection and Immunity in Society, UNSW, Sydney, NSW, Australia; St Vincent’s Hospital Sydney Centre for Applied Medical Research, Sydney, Australia 
10  St Vincent’s Clinical School, Faculty of Medicine, UNSW, Sydney, NSW, Australia; Division of Bone Biology, Garvan Institute of Medical Research, Sydney, NSW, Australia; School of Biotechnology and Biomolecular Sciences, Faculty of Science, UNSW, Sydney, NSW, Australia 
11  School of Life and Environmental Sciences and the Charles Perkins Centre, University of Sydney, Sydney, NSW, Australia 
Pages
1-14
Publication year
2018
Publication date
Aug 2018
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-018-05772-7
ProQuest document ID
2091749455
Copyright
© 2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.