Tnfrsf13b, encoding transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI), is a B cell-specific tumor necrosis factor (TNF) receptor superfamily member. It drives plasma cell differentiation, regulating various aspects of B cell responses [1,2,3,4].

In antibody deficiency syndromes, both biallelic and monoallelic TNFRSF13B mutations were identified in patients with common variable immunodeficiency disorders. Biallelic mutations were associated with hypogammaglobulinemia and impaired binding to a proliferation-inducing ligand (APRIL). Monoallelic changes, especially the C104R heterozygosity, increased the risk for common variable immunodeficiency disorders, and were associated with low numbers of IgD(-)CD27(+) B cells, benign lymphoproliferation, and autoimmune complications [1]. In addition, mice engineered with A144E variants of tnrsf13B (corresponding to human A181E) showed resistance to Citrobacter rodentium due to natural IgA deficiency in the intestine [2]. In organ transplantation, Tnfrsf13b mutations in mice led to early and severe antibody-mediated rejection (AMR) of cardiac allografts, through decreased "natural" IgM and compromised complement regulation [5].

In conclusion, Tnfrsf13b is crucial for B cell-mediated immune responses. Studies using mouse models have revealed its role in antibody deficiency syndromes, responses to enteric pathogens, and organ transplantation-related immune-mediated pathologies. Understanding Tnfrsf13b's functions provides insights into the mechanisms of these diseases and may inspire novel therapeutic strategies.