Macrophages direct location-dependent recall of B cell memory to vaccination

Rama Dhenni¹, Alexandra Carey Hoppé², Arnold Reynaldi³, Wunna Kyaw¹, Nathalie Tricia Handoko¹, Abigail K Grootveld¹, Yuki Honda Keith¹, Nayan Deger Bhattacharyya¹, Holly I Ahel¹, Aiden Josiah Telfser⁴, Andrew N McCorkindale⁵, Seyhan Yazar¹, Christina H T Bui⁶, James T Smith⁶, Weng Hua Khoo⁷, Mollie Boyd², Solange Obeid⁸, Brad Milner⁸, Mitchell Starr⁹, Fabienne Brilot¹⁰, Vanessa Milogiannakis², Anouschka Akerman², Anupriya Aggarwal², Miles P Davenport³, Elissa K Deenick¹¹, Christine L Chaffer⁶, Peter I Croucher⁶, Robert Brink¹², Leonard D Goldstein¹³, Deborah Cromer³, Stuart G Turville², Anthony D Kelleher¹⁴, Vanessa Venturi¹⁵, C Mee Ling Munier¹⁶, Tri Giang Phan¹⁷

Affiliations

¹ Precision Immunology Program, Garvan Institute of Medical Research, Sydney, NSW, Australia; St. Vincent's Healthcare Clinical Campus, School of Clinical Medicine, Faculty of Medicine and Health, UNSW Sydney, Kensington, Sydney, NSW, Australia.
² Immunovirology and Pathogenesis Program, Kirby Institute, UNSW Sydney, Sydney, NSW, Australia.
³ Infection Analytics Program, Kirby Institute, UNSW Sydney, Sydney, NSW, Australia.
⁴ Precision Immunology Program, Garvan Institute of Medical Research, Sydney, NSW, Australia.
⁵ Data Science Platform, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia.
⁶ St. Vincent's Healthcare Clinical Campus, School of Clinical Medicine, Faculty of Medicine and Health, UNSW Sydney, Kensington, Sydney, NSW, Australia; Cancer Plasticity and Dormancy Program, The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia.
⁷ Cancer Plasticity and Dormancy Program, The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia.
⁸ St. Vincent's Hospital Sydney, Sydney, NSW, Australia.
⁹ St. Vincent's Centre for Applied Medical Research, Sydney, NSW, Australia.
¹⁰ Brain Autoimmunity Group, Kids Neuroscience Centre, The Children's Hospital at Westmead, Faculty of Medicine and Health, School of Medical Sciences, Sydney, NSW, Australia; School of Medical Science, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia.
¹¹ Precision Immunology Program, Garvan Institute of Medical Research, Sydney, NSW, Australia; Immunovirology and Pathogenesis Program, Kirby Institute, UNSW Sydney, Sydney, NSW, Australia.
¹² Precision Immunology Program, Garvan Institute of Medical Research, Sydney, NSW, Australia; Immune Biotherapies Program, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia.
¹³ St. Vincent's Healthcare Clinical Campus, School of Clinical Medicine, Faculty of Medicine and Health, UNSW Sydney, Kensington, Sydney, NSW, Australia; Data Science Platform, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia.
¹⁴ Immunovirology and Pathogenesis Program, Kirby Institute, UNSW Sydney, Sydney, NSW, Australia; St. Vincent's Hospital Sydney, Sydney, NSW, Australia. Electronic address: akelleher@kirby.unsw.edu.au.
¹⁵ Immunovirology and Pathogenesis Program, Kirby Institute, UNSW Sydney, Sydney, NSW, Australia. Electronic address: vventuri@kirby.unsw.edu.au.
¹⁶ Immunovirology and Pathogenesis Program, Kirby Institute, UNSW Sydney, Sydney, NSW, Australia. Electronic address: cmunier@kirby.unsw.edu.au.
¹⁷ Precision Immunology Program, Garvan Institute of Medical Research, Sydney, NSW, Australia; St. Vincent's Healthcare Clinical Campus, School of Clinical Medicine, Faculty of Medicine and Health, UNSW Sydney, Kensington, Sydney, NSW, Australia. Electronic address: t.phan@garvan.org.au.

PMID: 40300604
DOI: 10.1016/j.cell.2025.04.005

Free article

Macrophages direct location-dependent recall of B cell memory to vaccination

Rama Dhenni et al. Cell. 2025.

Free article

. 2025 Jun 26;188(13):3477-3496.e22.

doi: 10.1016/j.cell.2025.04.005. Epub 2025 Apr 29.

Authors

Affiliations

¹ Precision Immunology Program, Garvan Institute of Medical Research, Sydney, NSW, Australia; St. Vincent's Healthcare Clinical Campus, School of Clinical Medicine, Faculty of Medicine and Health, UNSW Sydney, Kensington, Sydney, NSW, Australia.
² Immunovirology and Pathogenesis Program, Kirby Institute, UNSW Sydney, Sydney, NSW, Australia.
³ Infection Analytics Program, Kirby Institute, UNSW Sydney, Sydney, NSW, Australia.
⁴ Precision Immunology Program, Garvan Institute of Medical Research, Sydney, NSW, Australia.
⁵ Data Science Platform, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia.
⁶ St. Vincent's Healthcare Clinical Campus, School of Clinical Medicine, Faculty of Medicine and Health, UNSW Sydney, Kensington, Sydney, NSW, Australia; Cancer Plasticity and Dormancy Program, The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia.
⁷ Cancer Plasticity and Dormancy Program, The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia.
⁸ St. Vincent's Hospital Sydney, Sydney, NSW, Australia.
⁹ St. Vincent's Centre for Applied Medical Research, Sydney, NSW, Australia.
¹⁰ Brain Autoimmunity Group, Kids Neuroscience Centre, The Children's Hospital at Westmead, Faculty of Medicine and Health, School of Medical Sciences, Sydney, NSW, Australia; School of Medical Science, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia.
¹¹ Precision Immunology Program, Garvan Institute of Medical Research, Sydney, NSW, Australia; Immunovirology and Pathogenesis Program, Kirby Institute, UNSW Sydney, Sydney, NSW, Australia.
¹² Precision Immunology Program, Garvan Institute of Medical Research, Sydney, NSW, Australia; Immune Biotherapies Program, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia.
¹³ St. Vincent's Healthcare Clinical Campus, School of Clinical Medicine, Faculty of Medicine and Health, UNSW Sydney, Kensington, Sydney, NSW, Australia; Data Science Platform, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia.
¹⁴ Immunovirology and Pathogenesis Program, Kirby Institute, UNSW Sydney, Sydney, NSW, Australia; St. Vincent's Hospital Sydney, Sydney, NSW, Australia. Electronic address: akelleher@kirby.unsw.edu.au.
¹⁵ Immunovirology and Pathogenesis Program, Kirby Institute, UNSW Sydney, Sydney, NSW, Australia. Electronic address: vventuri@kirby.unsw.edu.au.
¹⁶ Immunovirology and Pathogenesis Program, Kirby Institute, UNSW Sydney, Sydney, NSW, Australia. Electronic address: cmunier@kirby.unsw.edu.au.
¹⁷ Precision Immunology Program, Garvan Institute of Medical Research, Sydney, NSW, Australia; St. Vincent's Healthcare Clinical Campus, School of Clinical Medicine, Faculty of Medicine and Health, UNSW Sydney, Kensington, Sydney, NSW, Australia. Electronic address: t.phan@garvan.org.au.

PMID: 40300604
DOI: 10.1016/j.cell.2025.04.005

Abstract

Vaccines generate long-lived plasma cells and memory B cells (Bmems) that may re-enter secondary germinal centers (GCs) to further mutate their B cell receptor upon boosting and re-exposure to antigen. We show in mouse models that lymph nodes draining the site of primary vaccination harbor a subset of Bmems that reside in the subcapsular niche, generate larger recall responses, and are more likely to re-enter GCs compared with circulating Bmems in non-draining lymph nodes. This location-dependent recall of Bmems into the GC in the draining lymph node was dependent on CD169⁺ subcapsular sinus macrophages (SSMs) in the subcapsular niche. In human participants, boosting of the BNT162b2 vaccine in the same arm generated more rapid secretion of broadly neutralizing antibodies, GC participation, and clonal expansion of SARS-CoV-2-specific B cells than boosting of the opposite arm. These data reveal an unappreciated role for primed draining lymph node SSMs in Bmem cell fate determination.

Keywords: SARS-CoV-2; affinity maturation; broadly neutralizing antibodies; germinal center; immune imprinting; memory; original antigenic sin; plasma cells; subcapsular sinus macrophage; vaccine.

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Conflict of interest statement

Declaration of interests The authors declare no competing interests.

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Macrophages direct location-dependent recall of B cell memory to vaccination

Affiliations

Macrophages direct location-dependent recall of B cell memory to vaccination

Authors

Affiliations

Abstract

Conflict of interest statement

MeSH terms

Substances

LinkOut - more resources

Full Text Sources

Medical

Molecular Biology Databases

Miscellaneous