Decoding Plasma Cell Maturation Dynamics with BCMA
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 intrinsic factors, the B cell maturation antigen (BCMA) has been implicated in APRIL-mediated survival of long-lived plasma cells. Therefore, we introduced a tdTomato reporter into the Tnfrsf17 (BCMA) locus, to decode the developmental steps behind the generation of mature plasma cell subsets. We demonstrate that the BCMA:Tom reporter is exclusively detected in plasma cells, with its expression differing between IgH isotypes and increasing with plasma cell maturity. Combined with a Blimp1-GFP reporter, the BCMA:Tom reporter allowed us to track the step-wise maturation from newly formed to late plasma cells in various plasma cell subpopulations. Notably, in vitro-stimulated B cells induce BCMA only after adoptive transfer into recipient mice, emphasizing the impact of the in vivo microenvironment in establishing a mature plasma cell compartment. The BCMA:Tom reporter mouse provides a robust 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. Overall design: Comparative gene expression profiling analysis of RNA-seq data for bone marrow plasma cell populations from Blimp1-GFP;BCMA:Tom reporter mice