GemPharmatech developed a transgenic mouse model, B6-hBAFF, with human B-cell-activating factor (BAFF) overexpression to study Systemic Lupus Erythematosus (SLE). Elevated BAFF levels in these mice increased immunoglobulin (Ig) and anti-dsDNA levels from early ages, accompanied by an expanded B cell population and reduced T cell ratio. By 25 weeks, B6-hBAFF mice exhibited lupus nephritis with characteristic renal abnormalities. Treatment with the anti-BAFF antibody Belimumab effectively reduced serum Igs and anti-dsDNA levels, improved kidney function, and decreased B and T cell populations. Additionally, treatments with Enpatoran and Orelabrutinib showed varying impacts on immune cell populations. This model demonstrates its utility for evaluating therapies targeting autoreactive B cells in SLE.