Hypergammaglobulinemia is a hall mark of Systemic lupus erythematosus (SLE) in patients and in mice. We have shown earlier that hypergammaglobulinemia is driven by both, increased formation and increased survival of antibody-secreting plasma cells that are relatively resistant to immunosuppressive therapy. Along with enlarged plasma cell populations, lupus patients and mice bearing the three major lupus susceptibility loci Sle1-3 exhibit increased megakaryopoiesis. Our preliminary data suggest that both phenomenons are linked via mutations in the c-mpl gene localized on Sle2. We hypothesize that mutation(s) in the c-mp pathway lead to increased megakaryopoiesis and in consequence to increased production of the anti-apoptotic cytokine IL-6 supporting plasma cell differentiation, survival and resistance to therapy. Here, we aim to probe this hypothesis further in lupus prone BcN mice carrying the Sle1-3 loci but are deficient in c-mpl, by blockade of IL-6/IL-6R and by searching for possible mutations in the c-mpl pathway and Sle2 related genes in our cohort of SLE patients.