Decoding plasma cell maturation dynamics with BCMA
Sebastian 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
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.