The role of Indoleamine 2,3-dioxygenase (IDO) in the survival of bone marrow resident long lived Plasma cells

Abstract Long lived plasma cells (LLPCs) are essential for sustained antibody responses and protective humoral immunity. How these cells maintain longevity and a durable antibody response is largely dependent on the complex nature of the bone marrow microenvironment in which these cells reside, and the pro survival factors produced in this niche. Previous work in our lab has shown that CD28 is required for LLPC survival, and we know that CD28 back signaling to CD80/86 induces IDO production from dendritic cells (DCs) within the bone marrow microenvironment. IDO is classically known to contribute to an immunosuppressive environment (specifically with respect to T cell activity). However, upon investigation of IDO in the normal setting, we observed fewer plasma cells present in the bone marrow of IDO knockout mice in comparison to wild type mice, as well as fewer antigen-specific plasma cells in the bone marrow following vaccination. Additionally, knowing the role of DCs in IDO production in the bone marrow, we employed the use of CD11c-DTR mice to observe the effects of PC survival upon DC elimination. We found that depletion of DCs significantly decreases the amount of antigen-specific plasma cells in the bone marrow. This leads us to propose a model where CD28, through back signaling to CD80/86 induces IDO production in DCs, a mechanism to maintain the bone marrow niche for long lived plasma cell survival and sustained antibody production.