Front Cover

Advances in Immunology

Copyright

Contents

Contributors

Chapter One: The Microglial Response to Neurodegenerative Disease

1. Introduction

2. A Unified View of Neurodegeneration-Associated Microglia

2.1. Identification of a Common Microglia Signature in Neurodegenerative Diseases

2.2. The Requirement for TREM2 in DAM Induction

2.3. The Role of ApoE in Amplifying the DAM Signature

2.4. Type I and Type II Interferons and DAM

3. Functions of DAM During Neurodegenerative Disease

3.1. Modulation of Pathological Protein Aggregates

3.2. Elimination of Synapses and Neurons

3.3. Activation of Neurotoxic Astrocytes

3.4. Summary

4. Genetic Implication of Microglia in Neurodegenerative Diseases

4.1. Rare Neurological Diseases Driven by Loss of Microglia

4.2. Alzheimer´s Disease

4.3. Other Neurodegenerative Diseases

5. Conclusions

Acknowledgments

References

Chapter Two: The First B-Cell Tolerance Checkpoint in Mice and Humans: Control by AID

1. Introduction

2. AICDA and AID

3. Phylogeny of AID Expression in Vertebrates

3.1. Lamprey

3.2. Amphibians

3.3. Birds

3.4. Mammals

4. AID Expression During Mouse B-Cell Development

4.1. Significance of Early AID Expression by Immature/T1 B Cells in Mice

4.2. Early AID Expression Supports CSR and SHM in Mouse Immature/T1 B Cells

4.3. AID as a Suppressor of Mouse B-Cell Development

4.4. AID Deficiency Is Associated With Systemic Autoimmunity

4.5. AID Mediates Central B-Cell Tolerance in Mice

4.6. Regulation of AID Expression in Immature/T1 B Cells

5. AID Expression in Human Immature B Cells

5.1. AID and RAG2 Coexpression in Human Immature B Cells

5.2. Human Central B-Cell Tolerance Depends on AID Expression

6. How Does AID Mediate Central B-Cell Tolerance?

6.1. Mechanisms of AID Tolerization in Humans

6.2. Mechanisms of AID Tolerization in Mice

7. Discussion

7.1. An Ancient Pathway for Controlling Receptor Specificity

7.2. Receptor Editing vs AID-Mediated Central Tolerance

7.3. Conclusions

References

Chapter Three: RAG Chromatin Scanning During V(D)J Recombination and Chromatin Loop Extrusion are Related Processes

1. Immunoglobulin Heavy and Light Chain Loci

2. V(D)J Recombination Mechanism

2.1. RAG Structure Provides Insights Into the V(D)J Recombination Mechanism

2.2. RSSs Restrict RAG-Joining Patterns Within IgH, IgL, and TCR Loci

2.3. Developmental Regulation of V(D)J Recombination

2.4. Accessibility Regulation of V(D)J Recombination

2.5. Chromosomal V(D)J Recombination Is Initiated From a V(D)J Recombination Center

2.6. The IGCR1 Looping Element Plays a Critical Role in Regulating IgH V(D)J Recombination

2.7. Striking Genomic Organization of CBEs Within the IgH Locus

3. Contact Loops Within the Genome May Often Be Formed by Chromatin Loop Extrusion

3.1. Orientation-Independent CBE-Based Loops Mediate V(D)J Recombination Within IgH

3.2. RAG-Dependent Chromosomal Translocations Provide Implications for a RAG Chromatin Scanning Mechanism

4. Robust New Genome-Wide Assays for Studies of V(D)J Recombination

4.1. HTGTS V(D)J Recombination Assay

4.2. 3C-HTGTS Provides a High-Resolution Assay for Revealing Chromatin Interactions in Antigen Receptor and Other Loci

5. RAG Unidirectionally Scans Chromatin of Endogenous Antigen Receptor Loci for Cleaving Substrates

5.1. RAG Scanning in Endogenous IgH and Tcr Loci

5.2. RAG Linearly Scans an IgH Subdomain Bounded by IGCR1 and the DJH RC

5.3. Proximal VH CBEs Enhance the Recombination Potential of Associated VHs by Enhancing Their Interaction With the DJH RC

5.4. RAG Scanning Is Likely Mediated by Cohesin-Mediated Loop Extrusion

5.5. CTCF-Mediated Loop Interactions and RAG in the Tcrd Locus

6. Broader Significance and Future Directions

Acknowledgments

Declaration of Interests

References

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