Advances in Immunology

Frederick W. Alt is a Howard Hughes Medical Institute (HHMI) Investigator and Director of the Program in Cellular and Molecular Medicine (PCMM) at Boston Children's Hospital (BCH). He is the Charles A. Janeway Professor of Pediatrics and Professor of Genetics at Harvard Medical School. He works on elucidating mechanisms that generate antigen receptor diversity and, more generally, on mechanisms that generate and suppress genomic instability in mammalian cells, with a focus on the immune and nervous systems. Recently, his group has developed senstive genome-wide approaches to identify mechanisms of DNA breaks and rearrangements in normal and cancer cells. He has been elected to the U.S. National Academy of Sciences, the U.S. National Academy of Medicine, and the European Molecular Biology Organization. His awards include the Albert Szent-Gyorgyi Prize for Progress in Cancer Research, the Novartis Prize for Basic Immunology, the Lewis S. Rosensteil Prize for Distinugished work in Biomedical Sciences, the Paul Berg and Arthur Kornberg Lifetime Achievement Award in Biomedical Sciences, and the William Silan Lifetime Achievement Award in Mentoring from Harvard Medical School.

Contributors

Early Steps of Follicular Lymphoma Pathogenesis 1. Follicular Lymphoma

2. The Classical Model of Follicular Lymphomagenesis

3. Circulating and Resident t(14;18) Cells Detected in Healthy Individuals are not Naive B-Cells

4. The “Allelic Paradox”: A Particular Immuno/Genophenotype of t(14;18)+ Activated B-Cells Which Does Not Match Any of the Physiological Memory Subsets Present in Blood

5. A Fraction of t(14;18) Cells in Healthy Carriers are Developmentally “Blocked” Follicular Lymphoma-Like Cells (FLLC)

6. BCL2, BCL6, Maturation Arrest, and the Role of the IgM Receptor

7. Trafficking, Early Dissemination, and Progression

8. A Protracted Model of Multi-Hit FL Genesis

9. Perspectives

Acknowledgments

“A Rose is a Rose is a Rose,” but CVID is Not CVID 1. Introduction

2. Definition and Diagnostic Criteria

3. Epidemiology

4. Pathophysiology/Immunopathology

5. Etiology/Genetics

6. CVID Classification Schemes

7. Clinical Presentation and Complications

8. Management

9. Prognosis and Survival

10. Summary

Role of Activation-Induced Cytidine Deaminase in Inflammation-Associated Cancer Development Abbreviations

1. Introduction: Cancer as a Genetic Disease

2. Nucleotide-Editing Enzymes as Inducers of Mutations

3. Physiologic Roles of AID in Antibody Production

4. Regulation of AID Expression in B Cells

5. Excessive AID Activity and Genetic Alterations Leading to Tumorigenesis

6. Roles of AID in Inflammation-Associated Human Carcinogenesis

7. Role of AID in the Development of Hematopoietic Malignancy

8. Conclusion

Acknowledgments

Comparative Genomics and Evolution of Immunoglobulin-Encoding Loci in Tetrapods 1. Introduction

2. Structure and Function of Antibodies

3. Ig-Heavy Chain in Tetrapods

4. Ig-Light Chains in Tetrapods

5. Evolution of Immunoglobulin J-Chain

6. Noncanonical Antibodies in Camelids

7. Concordance and Divergence of the Generation of Antibody Diversity

8. Concluding Remarks

Acknowledgments

Pax5 1. Pax5 and B Cell Commitment

2. Pax5 and the Control of Igh Rearrangements

3. Pax5 and Late B Cell Development

4. Role of Pax5 in B Cell Malignancies

5. Perspective

Acknowledgments