Factors Determining Clonal Selection in Germinal Centres

Most vaccines work by eliciting antibody-mediated immunity. Antibodies bind and “neutralize” important sites on pathogens, however achieving this represents an enormous challenge for B cells; it requires recognizing an almost infinite number of antigens, including many that are purposely difficult to reach. B cells overcome these hurdles by generating bespoke antibodies for each new infection they encounter through a remarkable process known as antibody affinity maturation that occurs within germinal centres (GCs). Here, GC B cells mutate their antibody-encoding genes and select those antibodies that bind best. However, the details of how selection occurs in GCs remains poorly understood. Using novel genetic tools that allow us to track the movement of cells between stages and events, we will investigate the fundamental principles underpinning this process. Antibody affinity maturation is often described as being a form of rapid Darwinian evolution; we hope to understand the selective pressures that drive this.