Pierre Ferrier
Aix Marseille Université,
Centre d'Immunologie de Marseille-Luminy

About this Book

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 simply considered as a private ground for a few aficionados, it can be seen as a way of understanding how mature lymphocytes 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 likely hijacked 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 and TCR) loci. This invader would itself have assigned the services of the nonhomologous end joining (NHEJ) DNA repair machinery as well as various DNA polymerases 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 our knowledge and beliefs. These are just the topics covered by the senior authors—all established leaders in this field—and their colleagues, whilst writing the various chapters in V(D)J Recombination. They lead us through the latest findings concerning the biochemical properties of the V(D)J recombinase (Swanson), its buried and potentially harmful transposase and translocase activities (Oettinger; Roth), the increasing importance of NHEJ, whose dysfunction causes severe forms of immune deficiencies (de Villartay), and the numerous facets in the control of gene rearrangement via non‑coding RNA transcription and exquisitely regulated changes in chromosomal structure (Corcoran; Feeney; Jouvin‑Marche; Krangel; Oltz and Spicuglia). Burning progress on regulatory aspects has included the large‑scale dynamics and nuclear compartmentalization of Ig and TCR loci (Singh), the anticipated—but difficult to ascertain—role of dedicated transcription factors (Zhang), the relationships between structural properties of the recombination core apparatus and its cell cycle phase‑dependant accumulation/degradation or connection to the chromatin template (Desiderio), the evolution of these regulatory aspects throughout the phylogeny (Hsu), and how abnormalities in the recombination apparatus/process can contribute to lymphoid malignancies (Macintyre). Overall, V(D)J Recombination represents a tour over this, in all respects, vital process and I would like to greatly acknowledge the efforts of these eminent colleagues for concisely describing its so many aspects. We believe that every advance in this field contributes to strengthening knowledge of fundamental importance both academically and clinically. Together, we hope that the result is an attractive book which will captivate its readers and encourage some to pursue further digging in this seemingly inexhaustible mine of biological resources.

Table of Contents

1. Early Steps of V(D)J Rearrangement: Insights 
from Biochemical Studies of RAG‑RSS Complexes
Patrick C. Swanson, Sushil Kumar and Prafulla Raval

2. Regulation of RAG Transposition
Adam G.W. Matthews and Marjorie A. Oettinger

3. Recent Insights into the Formation of RAG‑Induced Chromosomal Translocations
Vicky L. Brandt and David B. Roth

4. V(D)J Recombination Deficiencies
Jean‑Pierre de Villartay

5. Large‑Scale Chromatin Remodeling 
at the Immunoglobulin Heavy Chain Locus: 
A Paradigm for Multigene Regulation
Daniel J. Bolland, Andrew L. Wood and Anne E. Corcoran

6. Genetic and Epigenetic Control of V Gene 
Rearrangement Frequency
Ann J. Feeney

7. Dynamic Aspects of TCRa Gene Recombination:
 Qualitative and Quantitative Assessments 
of the TCRa Chain Repertoire in Man and Mouse
Evelyne Jouvin‑Marche, Patrizia Fuschiotti and Patrice Noël Marche

8. Germline Transcription: A Key Regulator 
of Accessibility and Recombination
Iratxe Abarrategui and Michael S. Krangel

9. Dynamic Regulation of Antigen Receptor 
Gene Assembly
Lance R. Thomas, Robin Milley Cobb and Eugene M. Oltz

10. Molecular Genetics at the T‑Cell Receptor b 
Locus: Insights into the Regulation 
of V(D)J Recombination
Marie Bonnet, Pierre Ferrier and Salvatore Spicuglia

11. Molecular Pathways and Mechanisms Regulating 
the Recombination of Immunoglobulin Genes 
during B‑Lymphocyte Development
Kristen Johnson, Karen L. Reddy and Harinder Singh

12. Regulation of V(D)J recombinationby E‑protein 
Transcription Factors
Mary Elizabeth Jones and Yuan Zhuang

13. Temporal and Spatial Regulation of V(D)J 

Yun Liu, Li Zhang and Stephen Desiderio

14. V(D)J Recombination: Of Mice and Sharks
Ellen Hsu

15. Normal and Pathological V(D)J Recombination: 
Contribution to the Understanding 
of Human Lymphoid Malignancies
Saïda Dadi, Sandrine Le Noir, Vahid Asnafi, Kheïra Beldjord 
and Elizabeth A. Macintyre