V(D)J Recombination

v(D)J recombination: for the community of immunologists and developmental biologists, the molecular route by which B and T lymphocytes acquire their unique function of affording adaptive immunity. Yet, for many-from experienced scientists to trainees-it represents a (rather too) sophisticated process whose true insight is excessively demanding. However, when not simplyconsidered as a private ground for a few aficionados, it can be seen as a way of understanding how maturelympho­ cytes carry on their basic functions. For the group of aficionados-which includes this editor-it is an elegant paradigm featuring many fascinating evolutionary achievements of which the biological world alone has the secret. These include a subtle biochemical principle most likelyhijacked some 470 million years ago from an ancestral gene invader and since then cleverly adapted by jawed vertebrates to precisely cleave and rearrange their antigen receptor (Ig andTCR)loci. This invader would itself have assigned the services of the nonhomologous end joining (NHEJ) DNArepair machinery as well as various DNApolymerases or transferases to work in concert with developmental clues in lymphoid cell lineages to generate an immune repertoire and efficient host surveillance while avoiding autoimmunity. Recently, important new refinements in these systems have emerged, continuing to challenge ourknowledge andbeliefs. These arejust thetopics covered by the senior authors-all established leaders in this field-and their colleagues, whilst writing the various chapters in V(D)J Recombination.

Early Steps of V(D)J Rearrangement: Insights from Biochemical Studies of RAG-RSS Complexes.- Regulation of RAG Transposition.- Recent Insights into the Formation of RAG-Induced Chromosomal Translocations.- V(D)J Recombination Deficiencies.- Large-Scale Chromatin Remodeling at the Immunoglobulin Heavy Chain Locus: A Paradigm for Multigene Regulation.- Genetic and Epigenetic Control of V Gene Rearrangement Frequency.- Dynamic Aspects of TCR? Gene Recombination: Qualitative and Quantitative Assessments of the TCR? Chain Repertoire in Man and Mouse.- Germline Transcription: A Key Regulator of Accessibility and Recombination.- Dynamic Regulation of Antigen Receptor Gene Assembly.- Molecular Genetics at the T-Cell Receptor ? Locus: Insights into the Regulation of V(D)J Recombination.- Molecular Pathways and Mechanisms Regulating the Recombination of Immunoglobulin Genes during B-Lymphocyte Development.- Regulation of V(D)J Recombination by E-Protein Transcription Factors.- Temporal and Spatial Regulation of V(D)J Recombination: Interactions of Extrinsic Factors with the RAG Complex.- V(D)J Recombination: Of Mice and Sharks.- Normal and Pathological V(D)J Recombination: Contribution to the Understanding of Human Lymphoid Malignancies.

PIERRE FERRIER is a Principal Investigator and Research Director at the

Centre d’Immunologie de Marseille-Luminy (CIML), France. He has also worked

as a Director of Marseille-Nice Genopole, a local consortium of more than twenty

laboratories aimed at developing high-throughput research techniques in genomics.

Main research interests include the analysis of the molecular mechanisms responsible

for the control of gene expression and recombination programs during hematopoietic

cell development and pathogenesis. He is a member of several national and international

scientific organizations including the Institut National de la Santé et de la

Recherche Médicale (Inserm), the Agence Nationale de la Recherche (ANR), the

Association pour la Recherche sur le Cancer (ARC), the Human Frontier Science

Program Organization (HFSPO), and the Université Virtuelle Médicale de Monaco

(UVMM). Pierre Ferrier received his academic degrees from Montpellier (MD) and

Marseille (PhD) Universities, France. He was a post-doctoral fellow (1986-90) in

the laboratory of Prof. F.W. Alt at the Columbia University College of Physicians

and Surgeons, New York, NY, USA.