Journal Article

Recruitment of plasma cells from IL-21-dependent and IL-21-independent immune reactions to the bone marrow

Hipfl, Christian, Guerra, Gabriela Maria, Mei, Henrik E., Wiedemann, Annika, Chen, Yidan, Cheng, Qingyu, Hein, Sascha, Hildt, Eberhard, Dörner, Thomas, Durek, Pawel, Matz, Mareen, Perka, Carsten, Witkowski, Mario, Lino, Andreia C., Schrezenmeier, Eva V., Mashreghi, Mir-Farzin, Ferreira-Gomes, Marta, Bondareva, Marina, Bauer, Laura, Niedobitek, Antonia, Rincon-Arevalo, Hector, Lehmann, Katrin, Kruglov, Andrey, Hardt, Sebastian, Ritter, Jacob, Radbruch, Andreas, Dang, Van Duc, Hutloff, Andreas, Heinrich, Frederik, Szelinski, Franziska, Melchers, Fritz, Stefanski, Ana-Luisa

2024

Overview

Bone marrow plasma cells (BMPC) are the correlate of humoral immunity, consistently releasing antibodies into the bloodstream. It remains unclear if BMPC reflect different activation environments or maturation of their precursors. Here we define human BMPC heterogeneity and track the recruitment of antibody-secreting cells (ASC) from SARS-CoV-2 vaccine immune reactions to the bone marrow (BM). Trajectories based on single-cell transcriptomes and repertoires of peripheral and BM ASC reveal sequential colonisation of BMPC compartments. In activated B cells, IL-21 suppresses CD19 expression, indicating that CD19 low -BMPC are derived from follicular, while CD19 high -BMPC originate from extrafollicular immune reactions. In primary immune reactions, both CD19 low - and CD19 high -BMPC compartments are populated. In secondary immune reactions, most BMPC are recruited to CD19 high -BMPC compartments, reflecting their origin from extrafollicular reactivations of memory B cells. A pattern also observable in vaccinated-convalescent individuals and upon diphtheria/tetanus/pertussis recall-vaccination. Thus, BMPC diversity reflects the evolution of a given humoral immune response. The mechanisms driving B cell differentiation into resident bone marrow plasma cells (BMPC) remain unclear. Here the authors use single cell sequencing and BMPC phenotyping to infer developmental pathways and regulation by IL-21 in germinal centres to promote maintenance of BMPC after vaccination in humans.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 13/1 / 13/21 / 13/31 / 38/91 / 42 / 49 / 631/250/1619/40/1742 / 631/250/2152/2153/1291 / 631/250/2152/2153/1571 / 631/250/2502 / 631/250/590/2293 / Adult / Antibodies / Antibody-Producing Cells - immunology / Antigens, CD19 - immunology / Antigens, CD19 - metabolism / B-Lymphocytes - immunology / Bone marrow / Bone Marrow - immunology / Bone Marrow Cells - cytology / Bone Marrow Cells - immunology / Bone marrow transplantation / CD19 antigen / Cell differentiation / Compartments / COVID-19 - immunology / COVID-19 - virology / Differentiation (biology) / Diphtheria / Diphtheria-Tetanus-Pertussis Vaccine - immunology / Female / Germinal centers / Heterogeneity / Humanities and Social Sciences / Humans / Humoral immunity / Immune response / Immune response (humoral) / Immune system / Immunity, Humoral - immunology / Immunological memory / Interleukin 21 / Interleukins - immunology / Interleukins - metabolism / Lymphocytes B / Male / Memory cells / Middle Aged / multidisciplinary / Pertussis / Phenotyping / Plasma cells / Plasma Cells - immunology / Public health / Recruitment / SARS-CoV-2 - immunology / Science / Science (multidisciplinary) / Severe acute respiratory syndrome coronavirus 2 / Single-Cell Analysis / Tetanus / Transcriptomes / Vaccination