The survival of B cells is compromised in kidney disease

Doureradjou Peroumal, Chetan V. Jawale, Wonseok Choi, Hossein Rahimi, Danielle Antos, De Dong Li, Shuxia Wang, Godhev K. Manakkat Vijay, Isha Mehta, Raymond West, Muthusamy Thangaraju, Thomas D. Nolin, Jishnu Das, John F. Alcorn, Partha S. Biswas

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article number10842
JournalNature communications
Volume15
Issue number1
DOIs
StatePublished - Dec 2024
Externally publishedYes

ASJC Scopus subject areas

  • General Chemistry
  • General Biochemistry, Genetics and Molecular Biology
  • General Physics and Astronomy

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