ABSTRACT
The maturation of B cells within the germinal centre (GC) is necessary for antigen-specific immune responses and memory. Dysfunction in the GC can lead to immunodeficiencies, autoimmune diseases, or lymphomas. Here we describe how recent advances in single-cell and spatial genomics have enabled new discoveries about the diversity of human GC B cell states. However, with the advent of these hypothesis-generating technologies, the field should now transition towards testing bioinformatic predictions using experimental models of the human GC. We review available experimental culture systems for modelling human B cell responses and discuss the potential limitations of different methods in capturing bona fide GC B cell states. Together, the combination of cell atlas-based mapping with experimental modelling of lymphoid tissues holds great promise to better understand the maturation of human B cells in the GC response and generate new insights into human immune health and disease.
Subject(s)
B-Lymphocytes , Cell Differentiation , Germinal Center , Humans , Germinal Center/immunology , B-Lymphocytes/immunology , Cell Differentiation/immunology , AnimalsABSTRACT
Drosophila melanogaster is unique among animal models because it has a fully defined synthetic diet available to study nutrient-gene interactions. However, use of this diet is limited to adult studies due to impaired larval development and survival. Here, we provide an adjusted formula that reduces the developmental period, restores fat levels, enhances body mass, and fully rescues survivorship without compromise to adult lifespan. To demonstrate an application of this formula, we explored pre-adult diet compositions of therapeutic potential in a model of an inherited metabolic disorder affecting the metabolism of branched-chain amino acids. We reveal rapid, specific, and predictable nutrient effects on the disease state consistent with observations from mouse and patient studies. Together, our diet provides a powerful means with which to examine the interplay between diet and metabolism across all life stages in an animal model.
