The mechanisms that drive impaired immunity in people with kidney disease remain unclear. A study by Partha Biswas and colleagues now links a uraemic toxin to defective germinal centre (GC) B cell responses in mice.

Gene-expression analysis and cell staining suggested reduced proliferation and increased apoptosis in GC B cells from KD mice compared with controls. In vitro, exposing plasmablasts to uraemic toxins at concentrations observed in people with advanced KD revealed that hippuric acid, which can bind to GPR109A (encoded by Niacr1), increased plasmablast apoptosis. The researchers showed that the GC response defect observed in animals with KD was dependent on the presence of GPR109A, as Niacr1–/– animals with AA-induced KD still had a normal GC response. Moreover, when B cell-deficient mice received Niacr1–/– B cells, induction of KD with AA did not compromise the number of NP-specific B cells detected after immunization.