V(D)J recombination

Correspondence to: David G. Schatz Howard Hughes Medical Institute Section of Immunobiology Yale University School of Medicine 300 Cedar Street, Post Box 208011 New Haven, CT 06520-8011, USA Tel. þ1-203-737-2255 Fax: þ1-203-785-3855 E-mail: david.schatz@yale.edu The discovery of V(D)J recombination (1, 2), nearly 30 years ago, triggered a dramatic shift in our thinking about somatic plasticity of the genome and fundamental features of the adaptive immune system. It opened the door to entirely new levels of investigation and understanding of the generation of antigen receptor diversity and lymphocyte development. Work in the 1980s focused on the antigen receptor loci; immunoglobulin heavy (IgH)and light chain-loci and Tcell receptor (TCR) a, b, g, and d loci were discovered and their structures and rearrangements catalogued (3). The next decade was ushered in with the discovery of the recombinationactivating gene 1 (RAG1) and RAG2 (4, 5), and during these 10 years, fundamental aspects of how the RAG proteins initiate V(D)J recombination were elucidated (6). The 1990s also saw the elaboration of the connection between V(D)J recombination and the ubiquitous process of non-homologous end-joining (NHEJ) (7), although the mechanisms by which the broken ends in V(D)J recombination get processed and repaired, remain poorly understood. The new decade of the 2000s is likely to be a transitional one in which important advances continue to be made in the study of the RAG proteins and the NHEJ repair process, but in which momentum gathers in the study of the higher order regulation of V(D)J recombination, an area inextricably linked to chromatin structure and to chromosome dynamics. This volume of Immunological Reviews contains 20 articles that discuss the current state of our knowledge in almost all areas relevant to V(D)J recombination and that highlight many of the major unanswered questions that can be glimpsed from our current vantage point. On the theory that it is important to know where you have come from as you consider where you are and where you are going, the volume begins with an article from the Litman laboratory that addresses the evolution of antigen receptor genes and the systems that diversify them. It is plausible that ‘split’ antigen receptor genes first arose through the action of Immunological Reviews 2004 Vol. 200: 5–11 Printed in Denmark. All rights reserved