A comparative study of adjuvants effects on neonatal plasma cell survival niche in bone marrow and persistence of humoral immune responses

• Published in: Frontiers in Immunology
• Main Authors: Pind, Auður Anna Aradóttir, Thorsdottir, Sigrun, Magnusdottir, Gudbjorg Julia, Meinke, Andreas, Del Giudice, Giuseppe, Jónsdóttir, Ingileif, Bjarnarson, Stefanía P
• Other Authors: Clinical Laboratory Services, Diagnostics and Blood Bank, Faculty of Medicine, Other departments
• Format: Article in Journal/Newspaper
• Language: English
• Published: 2022
• Subjects: Náttúrufræðingar; a proliferation inducing ligand (APRIL; TNFSF13); adjuvant; B cell maturation antigen (BCMA; TNFRSF17); comparative study; IL-6; neonatal vaccination; plasma cell survival niche; Oligodeoxyribonucleotides/metabolism; Adjuvants; Immunologic; Cell Survival; Tuberculosis Vaccines; Tetanus Toxoid; Animals; Immunity; Humoral; Interleukin-6/metabolism; Pharmaceutic/metabolism; B-Cell Maturation Antigen/metabolism; Mice; Plasma Cells; Tuberculosis/metabolism; Bone Marrow; Immunology and Allergy; Immunology; Iceland
• Online Access: https://hdl.handle.net/20.500.11815/3927; https://doi.org/10.3389/fimmu.2022.904415

Funding Information: AP was a recipient of a doctoral study grant from the University of Iceland Research Fund (2015-18). This study was financially supported by grants from the Icelandic Research Fund (130675051-53), The University of Iceland Research Fund (2018-20) and the Landspitali Science Fund (A-2017-068, A-2017-069, A-2018-076, A-2018-077, A-2019-084). Publisher Copyright: Copyright © 2022 Aradottir Pind, Thorsdottir, Magnusdottir, Meinke, Del Giudice, Jonsdottir and Bjarnarson. Copyright © 2022 Aradottir Pind, Thorsdottir, Magnusdottir, Meinke, Del Giudice, Jonsdottir and Bjarnarson. The neonatal immune system is distinct from the immune system of older individuals rendering neonates vulnerable to infections and poor responders to vaccination. Adjuvants can be used as tools to enhance immune responses to co-administered antigens. Antibody (Ab) persistence is mediated by long-lived plasma cells that reside in specialized survival niches in the bone marrow, and transient Ab responses in early life have been associated with decreased survival of plasma cells, possibly due to lack of survival factors. Various cells can secrete these factors and which cells are the main producers is still up for debate, especially in early life where this has not been fully addressed. The receptor BCMA and its ligand APRIL have been shown to be important in the maintenance of plasma cells and Abs. Herein, we assessed age-dependent maturation of a broad range of bone marrow accessory cells and their expression of the survival factors APRIL and IL-6. Furthermore, we performed a comparative analysis of the potential of 5 different adjuvants; LT-K63, mmCT, MF59, IC31 and alum, to enhance expression of survival factors and BCMA following immunization of neonatal mice with tetanus toxoid (TT) vaccine. We found that APRIL expression was reduced in the bone marrow of young mice whereas IL-6 expression was higher. Eosinophils, macrophages, megakaryocytes, monocytes and lymphocytes were important secretors of survival factors in ...