Project R-15069

Mechanisms of IgD-CD27- double negative B cell function and metabolism in aging (Research)

A continuous increase in global life expectancy and the number of aged individuals is related to high healthcare costs due to the coinciding increased prevalence of age-related diseases. Immune aging is characterized by a chronic pro-inflammatory status and has profound effects on the B cell compartment, including an increased prevalence of age-associated B cells. One of these ageassociated B cell populations, namely IgD-CD27- double negative (DN) B cells, presents with proinflammatory characteristics and is expanded in aged individuals, autoimmune and age-related diseases. However, the function of DN B cells and underlying mechanisms in aging remain unclear. Therefore, in this project, I aim to elucidate the mechanisms of DN B cells in aging. I hypothesize that specific signaling pathways underly a functional and metabolic shift of DN B cells in aging. First, I will study the transcriptome of DN B cells in healthy young, intermediate and aged subjects. Targets or pathways differentially expressed in aged subjects related to DN B cell function and metabolism will be further validated using ex vivo and in vitro experiments. This project will unravel the mechanisms underlying DN B cell function and metabolism during aging and will result in the identification and validation of novel DN B cell targets that are involved in aging-related processes.

01 October 2024 - 30 September 2028