Systemic Lupus Erythematosus (SLE) is an autoimmune disease mainly characterized by an overactivation of autoreactive lymphocyte which leads to the production of autoantibodies recognizing self-nucleic acids. This results in the formation of excessive immune complexes that settle in several organs and lead to inflammation and functional damages such as glomerulonephritis in the kidney. In order to investigate the mechanisms involved in SLE pathology we focused our studies on B cell and monocyte implication in our model of lupus-prone mice. We explored the role of the endosomal Toll-like receptor 8 (TLR8) in development of disease in lupus-prone mice and the key molecules involved in B cell differentiation and plasma cell survival, such as APRIL and its receptors TACI and BCMA. Our researches demonstrated two interesting pathways, one which is dependent to endosomal TLR and another which implicates TACI-dependent APRIL signaling. These pathways should be further explored with the hope that a deeper understanding could help to the development of novel effective therapies to treat human SLE.