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.

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.