Molecular Analysis of DNA Rearrangements in the Immune System

1. Front Matter

   Pages I-IX

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2. Initiation of V(D)J Recombination in a Cell-Free System by RAG1 and RAG2 Proteins

   • Dik C. van Gent, J. Fraser McBlane, Dale A. Ramsden, Moshe J. Sadofsky, Joanne E. Hesse, Martin Gellert

   Pages 1-10

3. rag-1 and rag-2: Biochemistry and Protein Interactions

   • David G. Schatz, Thomas M. J. Leu

   Pages 11-29

4. Regulation of Recombination Activating Gene Expression During Lymphocyte Development

   • Ulf Grawunder, Thomas H. Winkler, Fritz Melchers

   Pages 31-43

5. The Cell Cycle and V(D)J Recombination

   • Stephen Desiderio, Weei-Chin Lin, Zhong Li

   Pages 45-59

6. Double-Strand Breaks, DNA Hairpins, and the Mechanism of V(D)J Recombination

   • Sharri Bockheim Steen, Chengming Zhu, David B. Roth

   Pages 61-77

7. Identification of the Catalytic Subunit of DNA Dependent Protein Kinase as the Product of the Mouse scid Gene

   • Penny A. Jeggo, Stephen P. Jackson, Guillermo E. Taccioli

   Pages 79-89

8. The DNA-Activated Protein Kinase — DNA-PK

   • Carl W. Anderson, Timothy H. Carter

   Pages 91-111

9. Role of the Ku Autoantigen in V(D)J Recombination and Double-Strand Break Repair

   • Gilbert Chu

   Pages 113-132

10. Characterization of Chinese Hamster Cell Lines That are X-Ray-Sensitive, Impaired in DNA Double-Strand Break Repair and Defective for V(D)J Recombination

    • Sang Eun Lee, Dong Ming He, Eric A. Hendrickson

    Pages 133-142

11. Identification of the XRCC4 Gene: Complementation of the DSBR and V(D)J Recombination Defects of XR-1 Cells

    • Zhiying Li, Frederick W. Alt

    Pages 143-150

12. Developmental and Molecular Regulation of Immunoglobulin Class Switch Recombination

    • Matthias Lorenz, Andreas Radbruch

    Pages 151-169

13. Transcription Targets Recombination at Immunoglobulin Switch Sequences in a Strand-Specific Manner

    • Gregory A. Daniels, Michael R. Lieber

    Pages 171-189

14. Biochemical Studies of Class Switch Recombination

    • Rolf Jessberger, Matthias Wabl, Tilman Borggrefe

    Pages 191-202

15. Somatic Hypermutability

    • Matthias Wabl, Charles Steinberg

    Pages 203-219

16. Back Matter

    Pages 221-224

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The vertebrate immune system is distinctive among defense systems of multicellular organisms. In addition to nonspecific immunity, it generates a randomized array of millions of antigen receptors (immunoglobulins and T-cell receptors). A subset of these receptors are critical for binding to invading microbes or biochemicals from them to tag the microbes for elimination. Three site-directed DNA modification processes are critical to this process in vertebrates. V(D)J recombination generates the array of exons that encode the antigen binding pockets. Recent work summarized in this volume describes the dissection of this process at the biochemical level. The mechanism of the reaction is now understood in considerable detail. The proteins that catalyze many steps of the process have now been identified by biochemical and genetic recon­ stitution and by analysis of genetic mutants defective in V(D)J recombination. Class switch recombination is the process by which the variable domain exon of the heavy chain is changed from IgM to IgG, IgA. or IgE. Recent progress is described in the de­ velopment of an extrachromosomal substrate assay system. Molecular genetic analysis of the process in transgenics is defining some of the cis sequence requirements. Biochemical assays for defining enzymatic components are also described. In addition to exciting progress in V(D)J recombination and class switch recombination, one chapter describes recent pro­ gress in somatic hypermutation.

• DNA
• antigen
• biochemistry
• cell
• cell cycle
• gene
• gene expression
• immune system
• immunoglobulin
• mutation
• protein
• proteins
• receptor
• regulation
• transcription

• Institute for Immunology, Basel, Switzerland

  Rolf Jessberger

• Division of Molecular Oncology, Department of Pathology, Washington University School of Medicine, St. Louis, USA

  Michael R. Lieber

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