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...

The biological immune system exhibits powerful information processing capabil-ities, and therefore is of great interest to the computer scientist. A rapidly expanding research area has attempted to model many of the features inherent in the natural im-mune system in order to solve complex computational problems. This thesis examines the metaphor in detail, in an effort to understand and capitalise on those features of the metaphor which distinguish it from other existing methodologies. Two problem domains are considered — those of scheduling and data-clustering. It is argued that these domains exhibit similar characteristics to the environment in which the biological immune system operates and therefore that they are suitable candidates for application of the metaphor. For each problem domain, two distinct models are developed, incor-porating a variety of immunological principles. The models are tested on a number of artifical benchmark datasets. The success of the models on the problems considered confirms the utility of the metaphor. i

Evidence for somatic hypermutation of immunoglobulin genes has been observed in all the species in which immunoglobulins have been found. Previous studies have suggested that codon usage in Ig V genes is such that the sequence-specificity of somatic hypermutation results in greater mutability in complementarity-determining regions of the gene than in the framework regions. We have developed a new resampling-based methodology to explore genetic plasticity in individual V genes and in V gene families in a statistically meaningful way. We determine what factors contribute to this mutability difference, and characterize the strength of selection for this effect. We nd that although the codon usage in Ig V genes renders them distinct among translationally equivalent sequences with random codon usage, they are nevertheless far from being optimal in this regard. We find that the mutability patterns in a number of species are similar to those we find for human sequences. Interestingly, sheep seque...

High affinity memory cell production in the germinal centers. How far can selection reach?

This dissertation is approved, and it is acceptable in quality and form for publication on microfilm: Approved by the Dissertation Committee: Accepted:

Abstract: A general criterion is formulated in order to decide if recycling of B-cells exists in GC reactions. The criterion is independent of the selection and affinity maturation process and based solely on total centroblast population arguments. An experimental test is proposed to verify whether the criterion is fulfilled. 1 1

Abstract: A general criterion is formulated in order to decide if recycling of B-cells exists in GC reaction. The criterion is independent of the selection and affinity maturation process and based solely on total centroblast population arguments. An experimental test is proposed to check if the criterion is fulfilled. 1 1