Cluster of Differentiation 20 (CD20), encoded by the membrane spanning 4-domains A1 (MS4A1) gene, is a transmembrane phosphoprotein primarily expressed on the surface of B cells. Throughout B cell development, from pro-B cell to memory B cell stages, CD20 is expressed, but is absent in early pro-B cells and plasma cells ^[1]. Belonging to the MS4A family of four-transmembrane domain proteins, CD20 modulates B cell activation and proliferation by regulating calcium signaling, potentially acting as a calcium channel or co-receptor to amplify B cell receptor (BCR) responses ^[1]. As a key biomarker for B cell malignancies, including B-cell lymphomas, chronic lymphocytic leukemia, and hairy cell leukemia, CD20 serves as a target for therapeutic monoclonal antibodies such as rituximab and obinutuzumab, enabling the depletion of pathogenic B cells in autoimmune diseases and cancers ^[2-3]. Disruption of MS4A1 is associated with immunodeficiency common variable type 5 (CVID5), characterized by hypogammaglobulinemia, recurrent infections, and impaired antibody production due to aberrant B cell differentiation ^[4]. Recent studies have also revealed a role for CD20 in olfactory sensory neurons, where it mediates innate predator-avoidance behaviors in mice by detecting predator-derived odorants ^[5]. This dual functionality underscores the protein's significance in both immune regulation and sensory biology.

The B6-hCD20 mouse is a humanized model generated using gene editing technology to replace the entire base sequence of the mouse Ms4a1 gene in situ with the corresponding sequence from the human MS4A1 gene. Homozygous B6-hCD20 mice are viable and fertile. This model can be used for studying the pathological mechanisms and therapeutic approaches of autoimmune diseases and cancers, and for the development of CD20-targeted drugs.