Vdj Recombination

V(D)J Recombination: for the community of immunologists and developmentalbiologists, the molecular route by which B and T lymphocytes acquire their uniquefunction of affording adaptive immunity. Yet, for many--from experienced scientiststo trainees--it represents a (rather too) sophisticated process whose true insight isexcessively demanding. However, when not simply considered as a private groundfor a few aficionados, it can be seen as a way of understanding how mature lymphocytescarry on their basic functions. For the group of aficionados--which includesthis editor--it is an elegant paradigm featuring many fascinating evolutionaryachievements of which the biological world alone has the secret. These include asubtle biochemical principle most likely hijacked some 470 million years ago froman ancestral gene invader and since then cleverly adapted by jawed vertebrates toprecisely cleave and rearrange their antigen receptor (Ig and TCR) loci. This invaderwould itself have assigned the services of the nonhomologous end joining (NHEJ)DNA repair machinery as well as various DNA polymerases or transferases to workin concert with developmental clues in lymphoid cell lineages to generate an immunerepertoire and efficient host surveillance while avoiding autoimmunity.Recently, important new refinements in these systems have emerged, continuingto challenge our knowledge and beliefs. These are just the topics covered bythe senior authors--all established leaders in this field--and their colleagues, whilstwriting the various chapters in this book. They lead us through the latest findingsconcerning the biochemical properties of the V(D)J recombinase (Swanson), it'sburied and potentially harmful transposase and translocase activities (Oettinger;Roth), the increasing importance of NHEJ whose dysfunction causes severe formsof immune deficiencies (de Villartay), and the numerous facets in the control ofgene rearrangement via non-coding RNA transcription and exquisitely regulatedchanges in chromosomal structure (Corcoran; Feeney; Jouvin-Marche; Krangel;Oltz and Spicuglia).Burning progress on regulatory aspects has included the large-scale dynamicsand nuclear compartmentalization of Ig and TCR loci (Singh), the anticipated--butdifficult to ascertain--role of dedicated transcription factors (Zhang), the relationshipsbetween structural properties of the recombination core apparatus and its cell cycle phase-dependant accumulation/degradation or connection to the chromatintemplate (Desiderio), the evolution of these regulatory aspects throughout the phylogeny(Hsu), and how abnormalities in the recombination apparatus/process cancontribute to lymphoid malignancies (Macintyre).Overall, this book represents a tour over this, in all respects, vital process andI would like to greatly acknowledge the efforts of these eminent colleagues forconcisely describing its so many aspects. We believe that every advance in this fieldcontributes to strengthening knowledge of fundamental importance both academicallyand clinically. Together, we hope that the result is an attractive book which willcaptivate its readers and encourage some to pursue further digging in this seeminglyinexhaustible mine of biological resources.

PIERRE FERRIER is a Principal Investigator and Research Director at theCentre d’Immunologie de Marseille-Luminy (CIML), France. He has also workedas a Director of Marseille-Nice Genopole, a local consortium of more than twentylaboratories aimed at developing high-throughput research techniques in genomics.Main research interests include the analysis of the molecular mechanisms responsiblefor the control of gene expression and recombination programs during hematopoieticcell development and pathogenesis. He is a member of several national and internationalscientific organizations including the Institut National de la Sante et de laRecherche Medicale (Inserm), the Agence Nationale de la Recherche (ANR), theAssociation pour la Recherche sur le Cancer (ARC), the Human Frontier ScienceProgram Organization (HFSPO), and the Universite Virtuelle Medicale de Monaco(UVMM). Pierre Ferrier received his academic degrees from Montpellier (MD) andMarseille (PhD) Universities, France. He was a post-doctoral fellow (1986-90) inthe laboratory of Prof. F.W. Alt at the Columbia University College of Physiciansand Surgeons, New York, NY, USA.