Memory B cells are reactivated in subcapsular proliferative foci of lymph nodes

Imogen Moran, Akira Nguyen, Weng Hua Khoo, Danyal Butt, Katherine Bourne, Clara Young, Jana R. Hermes, Maté Biro, Gary Gracie, Cindy S. Ma, C. Mee Ling Munier, Fabio Luciani, John Zaunders, Andrew Parker, Anthony D. Kelleher, Stuart G. Tangye, Peter I. Croucher, Robert Brink, Mark N. Read and Tri Giang Phan ()
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Imogen Moran: Garvan Institute of Medical Research
Akira Nguyen: Garvan Institute of Medical Research
Weng Hua Khoo: Garvan Institute of Medical Research
Danyal Butt: Garvan Institute of Medical Research
Katherine Bourne: Garvan Institute of Medical Research
Clara Young: Garvan Institute of Medical Research
Jana R. Hermes: Garvan Institute of Medical Research
Maté Biro: UNSW
Gary Gracie: St Vincent’s Hospital
Cindy S. Ma: Garvan Institute of Medical Research
C. Mee Ling Munier: UNSW
Fabio Luciani: UNSW
John Zaunders: UNSW
Andrew Parker: St Vincent’s Hospital
Anthony D. Kelleher: UNSW
Stuart G. Tangye: Garvan Institute of Medical Research
Peter I. Croucher: UNSW
Robert Brink: Garvan Institute of Medical Research
Mark N. Read: University of Sydney
Tri Giang Phan: Garvan Institute of Medical Research

Nature Communications, 2018, vol. 9, issue 1, 1-14

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-05772-7

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