The survival of B cells is compromised in kidney disease.

The survival of B cells is compromised in kidney disease.

Publication date: Dec 30, 2024

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.

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Concepts Keywords
109a Animals
Apoptosis Apoptosis
Influenza B-Lymphocytes
Kidney Cell Survival
Models COVID-19
Disease Models, Animal
Female
Germinal Center
Humans
Immunity, Humoral
Kidney Diseases
Male
Mice
Orthomyxoviridae Infections
SARS-CoV-2

Semantics

Type Source Name
disease MESH kidney disease
disease MESH infections
pathway REACTOME Apoptosis
disease IDO toxin
disease MESH influenza
disease MESH virus infection
disease MESH comorbidity
disease IDO infection
drug DRUGBANK Pentaerythritol tetranitrate
disease IDO immune response
disease MESH Uremia
pathway REACTOME Immune System
disease IDO process
disease MESH infectious disease
pathway REACTOME Infectious disease
disease MESH complications
pathway REACTOME Influenza Infection
disease MESH defects
disease MESH chemically induced
disease MESH fibrosis
drug DRUGBANK Nitrogen
disease IDO assay
disease IDO production
disease IDO blood
drug DRUGBANK Proline
drug DRUGBANK Coenzyme M
drug DRUGBANK Aspartame
drug DRUGBANK Monomethyl fumarate
drug DRUGBANK Methylergometrine
disease IDO cell
disease MESH COVID-19
disease MESH Disease Models Animal
disease MESH Orthomyxoviridae Infections

Original Article

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