Mapping and modelling human B cell maturation in the germinal centre

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.