title: The relationship between hypothesis and experiment in unveiling the mechanisms of antibody gene diversification.
abstract: The origin of antibody diversity has intrigued scientists for nearly a century. We now know that the diversity is achieved through a 2-stage process. Gene rearrangement (catalyzed by the RAG1/2 recombinase) allows the production of a primary repertoire of antibodies; targeted deamination of cytosines within these rearranged antibody genes (catalyzed by the DNA deaminase AID) then allows them to be further diversified and matured by somatic hypermutation, gene conversion, and class-switch recombination. Here we review the history of the uncovering of some of these processes, contrasting the relative importance of hypothesis and methodological developments in driving the research at different periods of the work.
authors: Medical Research Council Laboratory of Molecular Biology, Cambridge, UK.
authors: Karuna
authors: K
authors: Ganesh
authors: Michael S
authors: MS
authors: Neuberger
mesh_terms: D000818:Animals; D000906:Antibodies / Q000235:genetics*; D000916:Antibody Diversity / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D003564:Cytidine Deaminase / Q000378:metabolism; D015321:Gene Rearrangement / Q000502:physiology; D005803:Genes, Immunoglobulin; D018398:Homeodomain Proteins / Q000502:physiology; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics; D018448:Models, Immunological; D027041:Somatic Hypermutation, Immunoglobulin / Q000502:physiology; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
chemical_list: D000906:Antibodies; D018398:Homeodomain Proteins; D007136:Immunoglobulins; C064658:RAG-1 protein; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase