How Your Immune System Learns

In humans’ immune response, B cells that produce high-affinity (strongly binding) antibodies are generated through a Darwinian evolutionary process called “affinity maturation”. Affinity maturation, which takes place in germinal centers (GCs), is driven by cycles of selection (mediated by T cells), division, and hypermutation of B cells. Recently, it was found that the T cells themselves also exhibit dynamic behavior throughout the course of the GC reaction, undergoing affinity-dependent proliferation. A model suggests that this reciprocal stimulation enforces a robust “homeostatic” regulation of the relative number of B cells and T cells in the GC, leading to a constant ratio of T cells to B cells. But the model also points to a problem: the high mutation rate of GC B cells can lead to “backsliding” of affinity. The proposed solution ??" a fitness-dependent mutation rate ??" has been experimentally verified, and has implications beyond B cell affinity maturation.

Speaker: Ned Windgreen, Princeton University