Decoding plasma cell maturation dynamics with BCMA

Sebastian R Schulz; Shannon R Menzel; Jens Wittner; Carolin Ulbricht; Alina T Grofe; Edith Roth; Ritu Mann-Nüttel; Stefanie Scheu; Andrew J Kueh; Alexander Jäck; Marco J Herold; Anja E Hauser; Katharina Pracht; Wolfgang Schuh; Hans-Martin Jäck

doi:10.3389/fimmu.2025.1539773

Decoding plasma cell maturation dynamics with BCMA

Front Immunol. 2025 Mar 11:16:1539773. doi: 10.3389/fimmu.2025.1539773. eCollection 2025.

Authors

Sebastian R Schulz^#¹, Shannon R Menzel^#¹, Jens Wittner¹, Carolin Ulbricht^{2

3}, Alina T Grofe^{2

3

4}, Edith Roth¹, Ritu Mann-Nüttel⁵, Stefanie Scheu^{5

6}, Andrew J Kueh^{7

8

9

10}, Alexander Jäck¹¹, Marco J Herold^{7

8

9

10}, Anja E Hauser^{2

3}, Katharina Pracht¹, Wolfgang Schuh¹, Hans-Martin Jäck¹

Affiliations

¹ Division of Molecular Immunology, Internal Medicine 3, University Hospital Erlangen, Nikolaus-Fiebiger Center, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany.
² Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Rheumatology and Clinical Immunology, Berlin, Germany.
³ Deutsches Rheuma-Forschungszentrum (DRFZ) Berlin, a Leibniz Institute, Berlin, Germany.
⁴ Institute of Chemistry and Biochemistry, Department of Biology, Chemistry and Pharmacy, Freie Universität Berlin, Berlin, Germany.
⁵ Institute of Medical Microbiology and Hospital Hygiene, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University of Düsseldorf, Düsseldorf, Germany.
⁶ Institute of Immunology, University Medical Center Rostock, Rostock, Germany.
⁷ Olivia Newton-John Cancer Research Institute, Melbourne, VIC, Australia.
⁸ School of Cancer Medicine, La Trobe University, Melbourne, VIC, Australia.
⁹ The Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, Australia.
¹⁰ Department of Medical Biology, University of Melbourne, Melbourne, VIC, Australia.
¹¹ Department of Neurology University Hospital, LMU Munich, Munich, Germany.

^# Contributed equally.

Abstract

Plasma cells provide protective antibodies following an infection or vaccination. A network of intrinsic and extrinsic factors fine-tunes the generation of a heterogenous plasma cell pool with varying metabolic requirements, transcriptional profiles and lifespans. Among these, the B cell maturation antigen (BCMA) has been implicated in the APRIL-mediated survival of long-lived plasma cells. To characterize the terminal maturation of plasma cells, we constructed a BCMA reporter mouse (BCMA:Tom) that exclusively labeled antibody-secreting cells and revealed that BCMA:Tom expression varied by IgH isotype and increased with plasma cell maturity. The BCMA reporter, used alongside the Blimp1-GFP reporter, also allowed detailed tracking of plasma cell development and highlighted the importance of the in vivo microenvironment to complete plasma cell maturation. Therefore, the BCMA:Tom reporter mouse provides a valuable tool for tracking plasma cell development and maturation with flow cytometry or advanced imaging techniques, enabling a deeper understanding of the mechanisms regulating plasma cell heterogeneity and longevity.

Keywords: BCMA (TNFRSF17); antibody-secreting cells (ASC); bone marrow; plasma cells; spleen; survival; thymus.

MeSH terms

Animals
B-Cell Maturation Antigen* / genetics
B-Cell Maturation Antigen* / immunology
B-Cell Maturation Antigen* / metabolism
Cell Differentiation* / immunology
Genes, Reporter
Mice
Mice, Inbred C57BL
Mice, Transgenic
Plasma Cells* / cytology
Plasma Cells* / immunology
Plasma Cells* / metabolism
Positive Regulatory Domain I-Binding Factor 1 / genetics
Positive Regulatory Domain I-Binding Factor 1 / metabolism

Substances

B-Cell Maturation Antigen
Positive Regulatory Domain I-Binding Factor 1