The BCMA:Tomato Mouse – a new reporter to characterize long-lived plasma cells

Abstract

Plasma cells provide humoral protection by secreting large amounts of antibodies. The heterogeneity of the plasma cell compartment has recently been demonstrated by functional studies and subpopulation markers, but the distinct properties of long-lived plasma cells (LLPC) are still unresolved. B Cell Maturation Antigen (BCMA) has been described as an essential receptor for LLPC survival. To elucidate the mechanisms of BCMA-mediated survival we established a reporter mouse line that expresses a tdTomato fluorescent protein together with BCMA under the control of the promoter of Tnfrsf17, the gene that encodes BCMA. In this reporter model, we could demonstrate the restricted expression of Tomato and BCMA in plasma cells making this an ideal system for the identification and tracking of plasma cells. Importantly, we observed an increase in the abundance of BCMA:Tomato along with a gradual loss of CD19 expression, delineating a developmental progression from plasmablasts to mature plasma cell subsets. In contrast, plasmablasts generated in vitro display only minimal BCMA induction, confirming the independence of BCMA expression from the Blimp1 master regulator of PC differentiation. In summary, we have developed a new plasma cell-specific reporter model that, together with an inducible BCMA-KO mouse, will allow us to investigate the BCMA-dependent signals of the generation and maintenance of LLPC. This work was supported, in part, by the Deutsche Forschungsgemeinschaft (DFG) through research grants TRR130 to H.-M.J. and W.S. and GRK1660 to H.-M.J.