Discovery of the mechanism for V(D)J hypermutation remains a basic goal of immunology despite the best efforts of many labo ratories. The existence of catalyzed, site-specific mutation and its exploitation for the somatic evolution of lymphocytes are re markable adaptations, yet since the discovery of hypermutation in 1970 (see cover), much hard work has generated little. Indeed, our knowledge of what is probably absolutely required for the mutator's action can be succinctly expressed: /g gene enhancers. Table 1 of Winter et a!.'s chapter puts into a historical perspec tive how our notions of the mutator have changed over the years. Despite these modest gains, most of us feel that this is the best of times. Our work has not only shown us what the mutator is not, it has also, like an artist's preliminary sketch, defined the questions and experiments we must face without diminishing the potential for new biology. In short, it is great fun to toil against a significant and enigmatic problem.
As knowledge from experimentation accumulates, we begin to have a somewhat clearer picture of the muation/conversion process(es). This volume takes one step forward in the analysis of somatic diversification.
List of Contents.- The Role of Promoter-Intron Interactions in Directing Hypermutation.- Somatic Hypermutation of Immunoglobulin Genes is Linked to Transcription.- On the Possible Role of Natural Reverse Genetics in the V Gene Loci.- Characteristics of Somatic Hypermutation of Human Immunoglobulin Genes.- Antibody Diversification in the Rabbit: Historical and Contemporary Perspectives.- Rabbit Appendix: A Site of Development and Selection of the B Cell Repertoire.- Affinity Maturation of the Primary Response by V Gene Diversification.- Lymphocyte Development and Selection in Germinal Centers.- Somatic Mutagenesis and Evolution of Memory B Cell.- Repertoire Diversification of Primary vs Memory B Cell Subsets.- Plasticity Under Somatic Mutation in Antigen Receptors.- Theoretical Limits to Massive Receptor Editing in Immature B Cells.- Clone: A Monte-Carlo Computer Simulation of B Cell Clonal Expansion, Somatic Mutation, and Antigen-Driven Selection.- Somatic Mutation in Ectothermic Vertebrates: Musings on Selection and Origins.