Abstract
With the advent of next-gen sequencing, it has been possible to study the antibody repertoire in unprecedented detail. Despite aquaculture supplying 50 percent of all seafood, repertoire analysis studies have largely been confined to mammals. Within the past five years, in addition to uncovering the stochastic and deterministic mechanisms that fashion the repertoire, these studies have also revealed how antigenic exposure can sculpt the antibody repertoire. All three chapters of this dissertation have the common goal of broadening our understanding from a narrow focus, largely on humans, mice, and domesticated mammals to one that encompasses distantly related phyla that have diverged millions of years ago. In Chapter 1, I focus on potential biases involved in Variable Diversity Joining (VDJ) recombination; Chapter 2 focuses on identifying VDJ combinations important in recognition of a hapten and the role affinity maturation plays in its recognition; Chapter 3 focuses on the dynamics of B cell populations following vaccination, which was only possible using information garnered from the second chapter. Significantly, this work revealed that biases in recombination play a critical role in shaping the IgT but not the IgM repertoire, vaccination drives public responses despite an apparent lack of affinity maturation, and antigenic exposure results in wholesale changes in the richness and evenness of the IgM repertoire as antigen-unresponsive populations contract and antigen-responsive populations expand. Aside from advancing our understanding of the evolution of adaptive immunity, this knowledge may eventually guide precision vaccine design, immunotherapeutics, and genetic selection programs to improve disease resistance.