Antibody producing plasma cells are maintained in the bone marrow for the lifetime of an individual, where they reside and provide long-term protection from invading pathogens. Plasma cells diseases such as Systemic Lupus Erythematosus (SLE) and Multiple Myeloma (MM) are characterised by the uncontrolled expansion of plasma cells in the bone marrow that in turn cause the accumulation of antibody in the periphery. Accumulating evidence suggests that survival of pathogenic plasma cells is influenced by supportive microenvironments within bone marrow. Furthermore, these microenvironments have been implicated as a major barrier in the long-term success of immunotherapies that targeted against plasma cells.

Here, we coupled lineage tracing models of SLE and MM with direct visualisation of plasma cell behaviour in situ using intravital imaging of bone marrow. These data are multiplexed with molecular profiling using HiDE and Seq (Hi-resolution Imaging of the Direct Environment with scRNA-Seq) and in situ spatial transcriptomics of mouse and human bone marrow. Using this approach, we have identified transcriptional deregulation of bone marrow microenvironments that occur in both a pathogenic plasma cell clone and therapy dependent manner.