The survival of B cells is compromised in kidney disease
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...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-12-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-55187-w |
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| author | 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 |
| author_facet | 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 |
| author_sort | Doureradjou Peroumal |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-4ad87ab755714ebe8b2a36f9cb4fc75a |
| institution | OA Journals |
| issn | 2041-1723 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-4ad87ab755714ebe8b2a36f9cb4fc75a2025-08-20T02:26:35ZengNature PortfolioNature Communications2041-17232024-12-0115111910.1038/s41467-024-55187-wThe survival of B cells is compromised in kidney diseaseDoureradjou Peroumal0Chetan V. Jawale1Wonseok Choi2Hossein Rahimi3Danielle Antos4De-dong Li5Shuxia Wang6Godhev K. Manakkat Vijay7Isha Mehta8Raymond West9Muthusamy Thangaraju10Thomas D. Nolin11Jishnu Das12John F. Alcorn13Partha S. Biswas14Division of Rheumatology and Clinical Immunology, Department of Medicine, University of PittsburghDivision of Rheumatology and Clinical Immunology, Department of Medicine, University of PittsburghDivision of Rheumatology and Clinical Immunology, Department of Medicine, University of PittsburghDivision of Rheumatology and Clinical Immunology, Department of Medicine, University of PittsburghDepartment of Immunology, University of PittsburghDivision of Rheumatology and Clinical Immunology, Department of Medicine, University of PittsburghDivision of Rheumatology and Clinical Immunology, Department of Medicine, University of PittsburghDepartment of Immunology, University of PittsburghDepartment of Immunology, University of PittsburghDepartment of Pharmacy and Therapeutics, University of PittsburghDepartment of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta UniversityDepartment of Pharmacy and Therapeutics, University of PittsburghDepartment of Immunology, University of PittsburghDepartment of Immunology, University of PittsburghDivision of Rheumatology and Clinical Immunology, Department of Medicine, University of PittsburghAbstract 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.https://doi.org/10.1038/s41467-024-55187-w |
| spellingShingle | 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 The survival of B cells is compromised in kidney disease Nature Communications |
| title | The survival of B cells is compromised in kidney disease |
| title_full | The survival of B cells is compromised in kidney disease |
| title_fullStr | The survival of B cells is compromised in kidney disease |
| title_full_unstemmed | The survival of B cells is compromised in kidney disease |
| title_short | The survival of B cells is compromised in kidney disease |
| title_sort | survival of b cells is compromised in kidney disease |
| url | https://doi.org/10.1038/s41467-024-55187-w |
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