The formation of germinal center (GC) response is crucial for antibody mediated immunity against infection. However, compromised humoral immunity to infection was seen in patients having pre-existing comorbid conditions including kidney disease. The mechanisms by which kidney disease account for poor antibody response is unknown. Here we show that kidney disease negatively impacted GC formation, antibody affinity maturation, isotype switching and titer. GC B cells exhibit increased apoptosis in kidney disease. Uremic toxin hippuric acid drives loss of mitochondrial membrane potential leading to increased apoptosis of GC B cells in G-protein–coupled receptor109A (Gpr109A) dependent manner. GC B cells express Gpr109A and mice without kidney disease treated with Gpr109A agonist exhibit similar defect in GC formation, affinity maturation and antibody titer. Conversely, immunized Gpr109A global knock-out or mice in which B cells are lacking Gpr109a show no defect in GC formation, affinity maturation and antibody titer following kidney disease. These results shed lights on hippuric acid/Gpr109A axis in causing GC B cells apoptosis and provide a mechanistic understanding of how renal dysfunction suppresses humoral immunity in patients with kidney disease.
Hippuric acid inhibits survival of germinal center B cells via GPR109A in kidney disease
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Poster and Podium (Block Symposium)
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Date: May 6 Presentation Time: 02:15 PM to 03:30 PM Room: Exhibit Hall F1