Molecular Analysis of B Lymphocyte Development and Activation (eBook)

Preface 5
Obituary 6
List of Contents 8
List of Contributors 9
Gene Regulatory Networks Orchestrating B Cell Fate Specification, Commitment, and Differentiation 10
1 Introduction 10
2 Specification and Commitment to the B Cell Fate 11
3 Regulation of Ig Gene Rearrangement and Pre-B Cell Differentiation 17
4 Conclusions and Perspectives 19
References 19
Helix-Loop-Helix Proteins in Lymphocyte Lineage Determination 23
1 Introduction 23
2 E2A Proteins 25
3 Class VI HLH Proteins: Hes-1/5 28
4 Id Proteins 28
5 Conclusions and Future Directions 29
References 32
Ikaros-Family Proteins: In Search of Molecular Functions During Lymphocyte Development 36
1 Introduction 37
2 Discovery 37
3 Structure and Family Members 38
4 Genetics 40
5 Localization to Centromeric Heterochromatin 42
6 Centromere Structure and Function 44
7 Centromere Role During Interphase 46
8 Potential Ikaros Functions at Pericentromeric Heterochromatin 47
9 Future Directions 49
References 50
Biochemistry of V(D)J Recombination 55
1 Introduction 56
2 DNA Transactions in V(D)J Recombination 59
3 Proteins That Mediate V(D)J Recombination 60
4 Recent Insights from In Vitro Cleavage Studies 68
5 Sequence-Specific Binding of the Recombination Signal by RAG1 and RAG2 73
6 Future Prospects 81
7 Epilogue 82
References 84
The pre-B cell Receptor in B Cell Development: Recent Advances, Persistent Questions and Conserved Mechanisms 92
1 Introduction 93
2 Commitment to the B Cell Lineage 94
3 The Development of Pre-B Cells 95
4 Initiating Signals Through the Pre-BCR 96
5 Different Signals for Different Functions 99
6 The Pre-TCR and Pre-BCR: Conservation of Signaling Properties and Functions? 101
7 Final Comments 102
References 103
Transcriptional Control of B Cell Activation 109
1 Introduction 110
2 Octamer-Binding Proteins and Cofactors 113
3 Rel-NF- kB Family Proteins 118
4 Pax-5/BSAP 123
5 Ets-1 Family Proteins 125
6 Ikaros Family Proteins 128
7 NF-AT Family Proteins 129
8 Other Transactivators Implicated in B Cell Activation 130
9 Concluding Remarks 134
References 136
Expression of MHC II Genes 151
1 Innate and Adaptive Immunity 152
2 Class II Transactivator 161
3 Conclusions and Future Directions 169
References 170
Class Switch Recombination: An Emerging Mechanism 175
1 Introduction 176
2 Overview of CSR 177
3 A Model for the Initiation and Resolution Steps in CSR 179
4 CSR and SHM Uncoupled 188
5 Genome Instability Syndromes and CSR 189
6 Targeting Mechanisms in CSR 191
7 Concluding Remarks 197
References 198
Blimp-1 Immunoglobulin Secretion and the Switch to Plasma Cells
1 Plasma Cell Biology 205
2 Transcriptional Regulation of Ig Secretion 208
3 Blimp-1-Regulated Maturation Program 212
4 Post-translational Regulation of Ig Secretion 220
5 Remarks and Future Directions 222
References 224
Wnt Signaling in Lymphopoiesis 228
1 Overview of the Different Wnt Signaling Pathways 229
2 The Canonical Wnt Signaling Pathway 230
3 Biochemical and Biological Properties of LEF/TCF Proteins 232
4 Activation of LEF1/TCF Function by b- Catenin and Other Cofactors 235
5 Transcriptional Repression and Inhibition of LEF1/TCF Function 237
6 Hematopoiesis 238
7 Role of the Wnt Pathway in Hematopoietic Stem Cells 240
8 Role of Wnt Signaling in Pro-B cell Proliferation and Survival 241
9 Role of Wnt Signaling in T Cell Development 243
10 Role of LEF/TCF in NK Cell Development 246
11 Concluding Remarks 247
References 247
Subject Index 256