Decoding Plasma Cell Maturation Dynamics with BCMA

Sebastian Schulz ¹ Shannon R Menzel ¹ Jens Wittner ¹ Carolin Ulbricht ^2,3 Alina T Liebheit ^2,3,4 Edith A Roth ¹ Ritu Mann-Nüttel ⁵ Stefanie Scheu ⁵ Andrew Kueh ^6,7,8,9 Alexander Jäck ¹ Marco Herold ^6,7,8,9 Anja Erika Hauser ^2,3 Katharina Pracht ¹ Wolfgang Schuh ¹ Hans-Martin Jäck ^1*

• ¹ Molecular Immunology, University of Erlangen Nuremberg, Erlangen, Bavarias, Germany
• ² German Rheumatism Research Center (DRFZ), Berlin, Baden-Württemberg, Germany
• ³ Charité University Medicine Berlin, Berlin, Baden-Wurttemberg, Germany
• ⁴ Institute of Chemistry and Biochemistry, Department of Biology, Chemistry and Pharmacy, Free University of Berlin, Berlin, Baden-Württemberg, Germany
• ⁵ Institute of Medical Microbiology and Hospital Hygiene, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University of Düsseldorf, Düsseldorf, Germany
• ⁶ Walter and Eliza Hall Institute of Medical Research, The University of Melbourne, Parkville, Victoria, Australia
• ⁷ Department of Medical Biology, University of Melbourne, Parkville, Australia
• ⁸ Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia
• ⁹ School of Cancer Medicine, La Trobe University, Bundoora, Australia

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.