The survival of B cells is compromised in kidney disease
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.
Authors
- Danielle Antos (ORCID: https://orcid.org/0000-0002-8451-0600)
- Isha Mehta (ORCID: https://orcid.org/0000-0002-6009-0787)
- Partha S. Biswas (ORCID: https://orcid.org/0000-0002-4570-7443)
- Thomas D. Nolin (ORCID: https://orcid.org/0000-0003-4339-1382)
- Doureradjou Peroumal (ORCID: https://orcid.org/0000-0003-2752-5686)
- Godhev K. Manakkat Vijay (ORCID: https://orcid.org/0000-0003-3833-3057)
- Wonseok Choi (ORCID: https://orcid.org/0000-0002-7566-6945)
- Dedong Li (ORCID: https://orcid.org/0000-0002-9474-390X)
- Raymond E. West (ORCID: https://orcid.org/0000-0002-6362-8837)
- Jishnu Das (ORCID: https://orcid.org/0000-0002-5747-064X)
- Muthusamy Thangaraju (ORCID: https://orcid.org/0000-0003-4202-1638)
- Chetan V. Jawale (ORCID: https://orcid.org/0000-0003-4621-6686)
- John F. Alcorn (ORCID: https://orcid.org/0000-0001-5997-7711)
- Shuxia Wang (ORCID: https://orcid.org/0000-0003-3102-2117)
- Hossein Rahimi
Institutions
- University of Pittsburgh (US)
- Augusta University (US)
- Stony Brook School (US)
- Stony Brook University (US)
Publication Details
- Journal
- Nature Communications
- Published
- 2024-12-30
- DOI
- https://doi.org/10.1038/s41467-024-55187-w
- Citations
- 9
- Primary Topic
- Renal Diseases and Glomerulopathies
- Type
- article
- Field-Weighted Citation Impact
- 3.05
Funders
- Division of Intramural Research, National Institute of Allergy and Infectious Diseases
- University of Pittsburgh
- National Institutes of Health
- Children's Hospital of Pittsburgh