The immune system uses many strategies to generate its enormous repertoire of diverse antibodies, but their relative importance is not understood. Here we address the contribution of antibody gene libraries to the antibody repertoire. We introduce a general framework, in which we can study many antibody-pathogen matching rules, including the widely-used shape-space model (Perelson and Oster, 1979). We use the genetic algorithm as a model of evolution to investigate the type of antibody repertoires that might evolve in relation to a given pathogenic environment. For the antibody/pathogen matching rules that we studied, the scaling relation between fitness and the size of the evolved antibody library is only a shifted variant of the scaling relation that we obtain with random libraries of the same size. We discuss how our results compare to the antibodies that are expressed in newborns, and we discuss the implications of our results for recent experiments with phage a...

In recent years significant progress has been made in defining the adult and neonatal B-cell repertoires. After Kreth and Williamson's isoelectric focusing analysis of the B-cell repertoire specific for 4-hydroxy-5-iodo-3-nitrophenacetyl in CBA mice (1), similar studies have investigated the responses to a large variety of haptenic, protein, and carbohydrate determinants in mice, rabbits, and guinea pigs (2-6). In toto, these studies, together with analyses of monoclonal antibodies and assessments of the frequency of B cells which represent identifiable specificities, indicate that the adult B-cell repertoire is extremely heterogeneous, and probably consists of greater than 107 unique antibody specificities (clonotypes) (6-8). The acquisition of the specificity repertoire during ontogenetic development poses problems and raises questions which are somewhat distinct from a similar analysis of the adult repertoire. Since the fetus and neonate are dynamic systems, one must define the B-cell repertoire at various points in ontogeny. Does the neonate have fewer specificities than the adult, since the individual perforce must start with fewer cells? How does the acquisition of the repertoire vary from individual to individual? Does antigen play a role