The survival of B cells is compromised in kidney disease
Doureradjou Peroumal, Chetan V. Jawale, Wonseok Choi, Hossein Rahimi, Danielle Antos, Dedong Li, Shuxia Wang, Godhev K. Manakkat Vijay, Isha Mehta, Raymond E. West, Muthusamy Thangaraju, Thomas D. Nolin, Jishnu Das, John F. Alcorn, Partha S. Biswas
Abstract
Antibody-mediated protection against pathogens is crucial to a healthy life. However, the recent SARS-CoV-2 pandemic has shown that pre-existing comorbid conditions including kidney disease account for compromised humoral immunity to infections. Individuals with kidney disease are not only susceptible to infections but also exhibit poor vaccine-induced antibody response. Using multiple mouse models of kidney disease, we demonstrate that renal dysfunction inhibits germinal center (GC) response against T-dependent antigens. 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 a G-protein–coupled receptor 109A dependent manner. Finally, GC B cells and antibody titer are diminished in mice with kidney disease following influenza virus infection, a major cause of mortality in individuals with renal disorders. These results provide a mechanistic understanding of how renal dysfunction suppresses humoral immunity in patients with kidney disease. Kidney disease compromises the humoral immune response to vaccines and infections. Here authors show in multiple murine kidney disease models that apoptosis of germinal center B cells via hippuric-acid-driven loss of mitochondrial membrane potential is a central cause of diminished antibody response.