How Germinal Centres Shape Serum Antibody Responses (360G-Wellcome-315850_Z_24_Z)

B cells undergo antibody affinity maturation in germinal centres (GCs) through rounds of somatic hypermutation and affinity-based selection. B cells detect antigen through their B cell receptors (BCRs) but lack a direct mechanism to measure binding affinity improvements. Instead, affinity is determined through competition: B cells with higher BCR affinity acquire more antigen and receive preferential support from a limited pool of T cells. Despite this, GCs support the co-maturation of many B cell lineages, often with substantial differences in BCR affinity. This raises a conundrum: how can affinity-based selection be both competitive and permissive? While the evolutionary benefits of diverse antibody responses are clear, the underlying mechanisms are not. Our research will investigate how B cells perceive relative BCR affinity differences in vivo, determining whether they tolerate or are blind to them. We will also explore the molecular processes that support the co-evolution of polyclonal B cell populations, clarifying the nature of the selection events. Additionally, since GC B cells do not secrete antibodies, we will examine how GCs decide the number of plasma cells to produce. Collectively, these studies will provide new insights into the fundamental processes shaping the quality and magnitude of humoral immunity.