CD20, a well-characterized B-cell surface marker, is central to B-cell activation and differentiation. In addition, it contributes to the pathogenesis of B-cell-mediated diseases, including lymphomas, rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE). Due to its selective expression on B cells, CD20 is an attractive target for therapeutic antibodies. Previously, we established an SLE model in transgenic mouse strains overexpressing human BAFF on a C57BL/6 mouse background (B6-hBAFF, T036794). To extend this platform for CD20-targeted drug evaluation, we generated a dual-humanized model by crossing B6-hBAFF with CD20 humanized mice (BALB/c-hCD20, T057498), resulting in the BAFF/CD20 dual-humanized mice (T065937).