T Regulatory Cells Support Plasma Cell Populations in the Bone Marrow

Long-lived plasma cells (PCs) in the bone marrow (BM) are a critical source of antibodies after infection or vaccination, but questions remain about the factors that control PCs. We found that systemic infection alters the BM, greatly reducing PCs and regulatory T (Treg) cells, a population that contributes to immune privilege in the BM. The use of intravital imaging revealed that BM Treg cells display a distinct behavior characterized by sustained co-localization with PCs and CD11c-YFP+ cells. Gene expression profiling indicated that BM Treg cells express high levels of Treg effector molecules, and CTLA-4 deletion in these cells resulted in elevated PCs. Furthermore, preservation of Treg cells during systemic infection prevents PC loss, while Treg cell depletion in uninfected mice reduced PC populations. These studies suggest a role for Treg cells in PC biology and provide a potential target for the modulation of PCs during vaccine-induced humoral responses or autoimmunity. [Display omitted] •Systemic infection induces a loss of plasma cells and Treg cells in the bone marrow•PCs and Treg cells share a niche with CD11c+ cells•Treg cells contribute to the regulation of PCs through CTLA-4•Treg cells promote the maintenance of long-lived PCs in the BM Glatman Zaretsky et al. find that long-lived PCs in the bone marrow share a niche with Treg cells and dendritic cells. Their data suggest a role for Treg cells in the maintenance and regulation of PC populations. Understanding PC-Treg cell interactions could provide strategies to treat immune-mediated diseases with PC involvement.