Evaluating the Logic of Selection in Germinal Centers

A central feature of vertebrate immune response is affinity maturation, wherein antibody-producing B cells undergo evolutionary selection in substructures of lymph nodes, called germinal centers. While it has been shown that the median B cell affinity dependably increases over the course of maturation, the exact logic behind this evolution remains vague. Three simple, potential selection methods include encouraging the reproduction of high affinity cells (“birth selection”), encouraging cell death in low affinity cells (“death selection”), and adjusting the mutation rate based on cell affinity (“mutational selection”). While all three forms of selection would lead to a net increase in affinity, different selection methods lead to distinct statistical dynamics. We discuss ramifications of different evolutionary models, and encourage thinking about evolutionary fitness as more than a singular number.