The BAFF gene, officially known as TNFSF13B (TNF Superfamily Member 13B), encodes the B-cell Activating Factor (also called BLyS or CD257), a type II transmembrane protein that is often proteolytically cleaved into a soluble, biologically active homotrimeric cytokine ^[1]. Primarily expressed by innate immune cells-including monocytes, macrophages, dendritic cells, and neutrophils-the BAFF protein is predominantly localized in secondary lymphoid tissues such as the spleen, lymph nodes, and tonsils, where it acts as a critical survival factor for B lymphocytes. By binding to its three cognate receptors (BAFF-R, TACI, and BCMA), it regulates the transition of immature B cells to mature status, maintains B-cell homeostasis, and promotes immunoglobulin class switching ^[2]. Dysregulation of the BAFF gene is clinically significant: its overexpression is a hallmark of systemic autoimmune diseases like Systemic Lupus Erythematosus (SLE), Rheumatoid Arthritis (RA), and Sjögren’s Syndrome, as well as B-cell malignancies such as Non-Hodgkin Lymphoma; conversely, its deficiency or underproduction can lead to Common Variable Immunodeficiency (CVID) due to a failure in B-cell maturation and antibody production ^[3]. The mouse Baff gene, inserted into the H11 "safe harbor" locus under the control of the alpha-1-antitrypsin (AAT) promoter, drives high, liver-specific expression. This results in elevated systemic levels of circulating BAFF, effectively mimicking the chronic B-cell hyperplasia and hypergammaglobulinemia seen in human autoimmune conditions ^[4].

H11-AAT-mBAFF(mTnfsf13b) mice are a model constructed using gene editing technology, where the Four copies of Human APOE enhancer-Human AAT promoter-Kozak-Mouse Tnfsf13b CDS-SV40 late pA cassette is inserted into the H11 locus. This model can be utilized for research into the pathological mechanisms and the development of therapeutic interventions for systemic autoimmune diseases (such as Systemic Lupus Erythematosus (SLE), Rheumatoid Arthritis (RA), and Sjögren’s Syndrome) as well as B-cell malignancies, including Non-Hodgkin Lymphoma.