B cell hyperactivities are involved in the development of systemic lupus erythematosus (SLE). Toll-like receptor 7 (TLR7) in the B cells plays a pivotal role in the pathogenesis of SLE. Previous studies have focused on the intrinsic role of B cells in TLR7/MyD88 signaling and consequently on immune activation, autoantibody production, and systemic inflammation. However, a feasible treatment for this immune disorder remains to be discovered. The in vitro cellular response that have been studied likely plays a central role in the production of some important autoantibodies in SLE. We successfully used R848 to build a lupus-like B cell model in vitro; these B cells were overactivated, differentiated into plasma cells, escaped apoptosis, massively proliferated, and produced large amounts of autoantibodies and cytokines. In the present study, we found that TJ-M2010-5, a novel MyD88 inhibitor previously synthesized in our lab, seemed to inhibit the lupus-like condition of B cells, including overactivation, massive proliferation, differentiation into plasma cells, and overproduction of autoantibodies and cytokines. TJ-M2010-5 also induce B cells apoptosis. Furthermore, TJ-M2010-5 was found to remarkably inhibit NF-kappa B and MAPK signaling. In summary, TJ-M2010-5 might correct R848-induced lupus-like immune disorders of B cells by blocking the TLR7/MyD88/NF-kappa B and TLR7/MyD88/MAPK signaling pathways.