Molecular biology of B cells:
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| Format: | Buch |
| Sprache: | English |
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Amsterdam [u.a.]
Elsevier [u.a.]
2015
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| Ausgabe: | 2. ed. |
| Schlagworte: | |
| Online-Zugang: | Inhaltsverzeichnis |
| Beschreibung: | XXII, 563 S. Ill., graph. Darst. |
| ISBN: | 9780123979339 |
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Datensatz im Suchindex
| _version_ | 1804152613551210496 |
|---|---|
| adam_text | Titel: Molecular biology of B cells
Autor: Honjo, T
Jahr: 2015
Contents
Preface
Contributors
1. The Structure and Regulation of
the Immunoglobulin Loci
Joseph S. Lucas, Cornells Murre, Ann J. Feeney
and Roy Riblet
XVII
xix
1.
2.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
Introduction
Genomic Organization of the Mouse
Immunoglobulin Heavy Chain Locus
Genomic Organization of the
Mouse Immunoglobulin Kappa
Light Chain Locus
Genomic Organization of the
Mouse Immunoglobulin
Lambda Light Chain Locus
B Cell Development and Regulation
of V(D)J Recombination
Junctional Diversity
Combinatorial Diversity
Noncoding Transcription and
Immunoglobulin Locus Rearrangement
The Process of Dh-Jh Recombination
Epigenetics and Immunoglobulin Locus
Rearrangement
Insulators and Immunoglobulin Locus
Rearrangement
3D Structure and Compaction of the
Immunoglobulin Heavy Chain Locus
Conclusion
References
2. The Mechanism of V(D)J
Recombination
Alicia J. Little, Adam Matthews, Marjorie
Oettinger, David B. Roth and David G. Schatz
1. Overview
2. Antigen Receptor Gene Assembly
3. Recombination Signal Sequences
4. Biochemistry of V(D)J Cleavage
5. RAG1 and RAG2
6. A Role for HMGB1 in V(D)J
Recombination
3
5
5
6
6
6
7
7
7
8
13
13
15
16
17
18
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
Recombination Complexes: Analysis
of Stoichiometry and Organization
V(D)J Recombination Is Tightly Regulated
during Lymphocyte Development
Accessibility Model of Regulation
Overview of Chromatin Structure
Regulation by Nucleosome Structure
and Histone Acetylation
Regulation by Histone Methylation
How Is the Chromatin Structure of
Antigen Receptor Loci Developmentally
Regulated?
Additional Layers of Regulation
Regulation of V(D)J Recombination:
Summary
Oncogenic Lesions in Lymphoid
Neoplasms: The Price of a
Diverse Antigen Receptor Repertoire
Proposed Mechanisms Underlying
RAG-Mediated Genomic Lesions
17.1 Recognition Errors: Ectopic
Recombination between cRSS
17.2 Recognition Errors: RAG-Mediated
Cleavage at Non-B-Form DNA
Structures
17.3 Joining Errors: End Donation
17.4 Joining Errors: Transposition
Regulatory Controls Proposed to Suppress
RAG-Mediated Genomic Instability
18.1 Control Cell Type and Developmental-
Stage-Specific Expression of
Recombination Activity
Restrict RAG Activity to an
Appropriate Stage of the Cell Cycle
Suppress Recognition of Inappropriate,
Ectopic Target Sequences
Downregulate RAG s Inherent
Transposition Activity
Suppress Interchromosomal V(D)J
Recombination
Regulate Joining: Ensure High-Fidelity
cNHEJ Machinery Is Used and
Discourage End Donation
V(D)J Recombination Errors as Pathogenic
Lesions in Lymphoid Neoplasms: Summary
References
18.2
18.3
18.4
18.5
18.6
19
20
21
21
21
22
22
23
23
24
24
24
25
26
26
26
26
26
27
27
27
27
28
28
VII
vili
Contents
3. Transcriptional Regulation
of Early B Cell Development
James Hagman
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
PU.1 Sets the Stage for Lymphoid and
Myeloid Development 35
Lineage Priming in Lymphoid Progenitors
by Ikaros 38
E2A Regulates the Chromatin Landscape
to Promote Gene Expression in B Cell
Development 39
E2A Is Inhibited by Id Proteins 41
lnterleukin-7/Stat5 Signaling
Provides an Early Signal for B Cell
Lineage Specification 41
Early B Cell Factor: Central Coordinator
of B Cell Development 42
Collaboration between EBF1 and Foxol 43
Regulation of the B Cell-Specific
Program by Pax5 44
Regulation of B Lineage Commitment 46
Conclusion 47
Acknowledgment 47
References 47
4. Relationships among B Cell
Populations Revealed by Global Gene
Analysis
Van Zhou, Byoung-Gon Moon, Susan A. Shinton,
Kyoko Hayakawa and Richard R. Hardy
1. Introduction
2. Gene Profile Changes with B Cell
Maturation Suggest an Ordering of
Transitional Stages
3. Distinctions in Gene Networks Activated
in Mature B Cell Populations
4. Fo/B2 B Cells in Different Tissues are
Similar, but Specialization with
Location Emerges
5. Conclusions
Acknowledgment
References
5. Roles of MicroRNAs in B Lymphocyte
Physiology and Oncogenesis
Stefan A. Muljo and Klaus Rajewsky
55
55
58
60
61
63
63
65
1. Introduction
2. Control of Cell Survival and Proliferation
by miR-17~92 in B Cell Development and
Lymphomagenesis
3. The Problem of miRNA Target Identification
and Validation 68
4. miR-155 in Germinal Center B Cells and
Lymphomagenesis 68
5. Discovery of an Elusive Tumor Suppressor:
miR-15a~16-1 Cluster 69
6. Lin28b Regulates the Fetal-Adult B Cell
Development Switch 69
7. To Be Further Determined 70
8. Concluding Remarks 71
Acknowledgments 71
References 71
66
Proliferation and Differentiation
Programs of Developing B Cells
Markus Werner and Hassan Jumaa
1. Proliferation and Differentiation Programs
at the Pro-B Cell Stage
1.1 The IL-7R
1.2 SOCS are Negative Regulators of
IL-7R Signaling
1.3 Human B Cells Develop
Independently of the IL-7R
1.4 IL-7R Signaling and the Proliferation
of Pro-B Cells
1.5 IL-7R Signaling and the Survival of Pro-B
Cells
1.6 The Role of IL-7R in Inducing
Differentiation Programs
2. Proliferation and Differentiation Programs
at the Pre-B Cell Stage
2.1 Signal Induction from the
Pre-BCR
2.2 Signals from the Pre-BCR Induce
Both Proliferation and Differentiation
of Pre-B Cells
2.3 Role of Class IA PI3K in
Pre-BCR-lnduced Proliferation
2.4 Regulation of Survival and Cell
Cycle by the Class IA PI3K
Downstream Target AKT
2.5 The Family of FoxO Transcription
Factors is a Highly Conserved
Downstream Target of PI3K Signaling
2.6 Differentiation of Pre-B Cells
Involves Allelic Exclusion of the
IgH Gene Locus
2.7 Pre-BCR Signals Induce Differentiation
by Activating SLP-65-Dependent
Signaling Pathways
2.8 SLP-65-Dependent Signaling
Promotes IgL Gene Recombination
and Differentiation
2.9 Interplay of the Proliferation and
Differentiation Programs at the Pre-B
Cell Stage
76
76
77
77
78
78
79
80
80
80
81
82
83
83
84
86
86
Contents
2.10 The Conventional BCR Replaces the
Pre-BCR in Providing Survival Signals 87
3. Selection Mechanisms at the Immature
B Cell Stage 88
3.1 Role of Self-Reactivity in Early B Cell
Development 88
3.2 The Role of BCR Signaling in the
Differentiation of Peripheral B Cells 90
3.3 The Role of BCR Signaling in Malignant
Transformation of B Cells 90
References 91
7. Development and Function of B Cell
Subsets
Andre M. Vale, John F. Kearney, Alberto Nobrega
and Harry W. Schroeder
1. Introduction 99
2. B-1, Marginal Zone and Follicular B Cells 99
2.1 Introduction to the Three Subsets 99
3. Mechanisms for the Compartmentalization
of B-Cell Subsets 103
3.1 Ontogeny 103
3.2 B-1 Cells 104
3.3 The Spleen 105
3.4 FOB Cells 106
3.5 MZ B Cells 106
3.6 Chemokines 107
3.7 B-Cell Growth and Survival Factors 108
4. Selection and Differential Survival Mechanisms: BCR Signaling, Composition,
and Specificity 109
4.1 BCR Signaling 109
4.2 BCR Composition 110
4.3 BCR Specificity 111
4.4 Microbial Exposure 111
4.5 T-lndependent Signals 111
5. Other Factors Involved in the Formation
of B-Cell Subsets 112
5.1 Role of CD5 112
5.2 Apoptosis 112
6. Homeostasis of B-Cell Subsets
and Repertoires 112
7. Conclusion 113
Acknowledgment 113
References 113
8. B Cells and Antibodies in Jawless
Vertebrates
Brantley R. Herrin, Masayuki Hirano, Jianxu Li,
Sabyasachi Das, Yoicbi Sutoh and Max D. Cooper
1. Introduction 121
2. Lampreys and Hagfish Have Three Types
of VLRGenes 121
ix
3. VLR Gene Assembly Mechanism and
Sequence Diversity 121
4. Lamprey CDA1 and CDA2 124
5. VLRA, VLRB, and VLRC Are Expressed
by Different Lymphocyte
Populations 124
6. Characterization of B-Like and
Two T-Like Lymphocyte Populations
in Cyclostomes 124
7. VLRA+, VLRB+ and VLRC+ Cells Have
Distinct Gene Expression Profiles 125
8. Generation of the T-Like and B-Like Cells
in Lampreys 126
9. The Unique Structure of VLRB
Antibodies 12 7
10. VLRB Monoclonal Antibodies 127
11. Structure of VLR Antigen-Binding
Domains 128
12. Structures of VLRB Antibody-Antigen
Complexes 129
13. Conclusion 130
References 131
9. The Origin of V(D)J Diversification
Ellen Hsu and Susanna M. Lewis
1. The Alien Seed 133
1.1 Transposons and Transposition 133
1.2 Horizontal Transfer 134
1.3 Exaptation 136
1.4 Modus Operandi 136
1.5 Structure and Linkage of RAG1 and
RAG2 Genes 137
1.6 Fossil Transposons 137
1.7 RAG2-like Gene in Sea Urchin 137
1.8 Current Questions: Transposon
Origins, Horizontal Transfer,
and Exaptation 139
2. The Evolution of BCR and TCR Loci 139
2.1 Germline Coding Joint Formation:
V(D)J Gene Segment Fusions 139
2.2 Germ Line Signal Joint Formation: the
Creation of D Segments 141
2.3 Germ Line Hybrid Joint Formation:
RSS Swaps and Locus
Speciation 142
3. Considerations on the ur-V Gene 142
3.1 Rearrangement Generates Sequence
Length Diversity 142
3.2 Considering Jawless Fishes 144
3.3 Hypermutation in Evolution 145
3.4 An Innate Defense V Gene 145
4. Concluding Remarks 146
Acknowledgments 146
References 146
X
Contents
10. Structure and Signaling Function of
the B-Cell Antigen Receptor and Its
Coreceptors
Michael Reth, Lars Nitschke, Masaki Hikida and
Tomohiro Kurosaki
1. Introduction 151
2. Basic Structure of the BCR Complex 151
3. BCR Activation Models 153
4. The Resting State of the BCR 154
5. Interaction of the BCR with
Signal-Transducing Kinases and Adaptors 155
6. BCR Coreceptors CD19 and CD22 156
7. CD19 Functions in a Complex with CD21
and CD81 156
8. Signaling by the CD19 Tail 157
9. Human Mutations in the CD19/CD21/CD81
Complex 158
10. CD22: An Inhibitory Receptor 158
11. Regulation of CD22 Signaling by Ligand
Interactions 160
12. The Role of CD22 in Preventing
Autoimmunity 161
13. BCR-Controlled Signaling Processes 161
14. BCR-Mediated Adaptor and PLCy2
Activation 161
15. IP3 Promotes Calcium Release and Activation
of Nuclear Factor of Activated T Cells 162
16. DAG and Nuclear Factor-icB Activation 163
17. Activation of the PI3K Pathway 163
18. Akt and Foxo Regulation 164
Acknowledgment 164
References 164
11. Fc and Complement Receptors
Jeffrey V. Ravetch, Falk Nimmerjahn and
Michael C. Carroll
1. Consequences of FcyRIIB Deficiency 171
2. Consequences of Complement and
Complement Receptor Deficiencies 173
3. Fc Receptors 173
3.1 Expression Pattern and Signaling
Properties of FcyRIIB 173
3.2 ITI M Pathways 174
3.3 Affinity Maturation 176
3.4 Ig Enhancement and Suppression 177
3.5 Memory Response 177
3.6 Plasma Cell Homeostasis 177
3.7 CD23 178
3.8 FCR-Like Proteins 178
3.9 Fcp-Receptor 178
4. Complement Receptors 179
4.1 Early Components of Complement
Influence the Humoral Response 179
4.2 Regulation of Complement Receptors 179
4.3 CD21 Forms a Co-receptor on B Cells 179
4.4 CD21/CD35 Regulate B-Cell Responses 180
5. Coreceptor Signaling versus Antigen
Localization to FDCs 180
5.1 B Cells Require Complement
Receptors at Five Different Stages 181
6. Frontiers: Complement versus Fc Receptors 183
References 184
12. B Cell Localization and Migration
in Health and Disease
Anja E. Hauser and Uta E. Höpken
1. Introduction 187
2. Migration of B Cells in the Bone Marrow 188
2.1 Migration and Interactions of
Developing B Cells 188
2.2 Mature B Cells and Immune Responses
in the Bone Marrow 189
3. Migration of B Cells into and within SLOs 189
3.1 Microanatomical Structure of SLOs
and Mechanisms of B Cell Entry 189
3.2 Migration of B Cells within SLOs 193
4. Location and Migration of
Antibody-Secreting Cells 197
5. Body Cavity B-1 B Cell Trafficking 199
6. Mucosal B Cell Migration 200
7. Homing of B Cells during Chronic
Inflammation and Tertiary Lymphoid
Organ Formation 202
8. Migration of Neoplastic B Cells 203
9. Conclusion 206
References 206
13. B Cells as Regulators
Ping Shen, Ellen Hilgenberg, Andreia C. Lino,
Van Due Dang, Stefanie Ries, Imme Sakwa
and Simon Fillatreau
1. Introduction 215
2. Regulatory Role of B Cells in UC 215
3. Protective Function of B Cells in EAE 217
4. Regulatory Roles of B Cells in Systemic
Lupus Erythematosus 219
5. Regulatory Role of B Cells in Bacterial
Infections 220
6. Characterization and Function of
IL-10-Producing B Cells in Humans 221
Contents
xi
7. Concluding Remarks 222
Conflict of Interest 222
Acknowledgments 222
References 222
14. B Cell Memory and Plasma
Cell Development
14a. Generation of Memory B Cells
Toshitada Takemori
1. Memory B Cell Markers 227
2. Properties of Memory B Cells 227
3. Diversity within the Memory
Compartment 227
4. Dynamics in B Cell Response toward
Memory Formation 228
5. Selection of High-Affinity Memory B
Cells in CCs 228
6. How Memory B Cells Develop in the GC
Reaction 229
7. GC-lndependent Memory B Cells 229
8. GC-lndependent and -Dependent
Memory B Cells Develop with the
Help of Different T-Cell Subsets 229
9. GC-lndependent and -Dependent Memory
B Cells Are Involved in the Secondary
Response 230
References 230
14b. Plasma Cell Biology
David Tarlinton
1. Introduction 232
2. Plasma Cell Subsets 233
2.1 Plasmablasts 233
2.2 Plasma Cells 233
3. Cellular Aspects of Plasma Cell
Differentiation 234
3.1 B1 Cells, Natural Antibody, and
Plasma Cell Differentiation 234
3.2 TI Immune Responses 235
3.3 a-GalCer 236
3.4 TD Immune Responses and
Extrafollicular Foci 236
3.5 TD Immune Responses and CCs 237
4. Molecular Biology of Plasma Cell
Differentiation 239
5. Plasma Cell Survival 240
6. Plasma Cell Survival Molecules 241
References 241
14c. Memory Plasma Cells
Falk Hiepe and Radbruch Andreas
1. How Does the Pathogenic Plasma
Cell Memory Arise? 244
2. Plasma Cell Niches 245
3. How to Target Memory Plasma Cells 246
4. Direct Plasma Cell Targeting 246
References 248
15. The Role of the BAFF and Lymphotoxin
Pathways in B Cell Biology
Fabienne Mackay and Jennifer L. Commerman
1. BAFF/APRIL: Important Regulators of B Cell
Survival, Homeostasis, and Function 251
1.1 Introduction 251
1.2 The BAFF-APRIL System 251
1.3 The Role of the BAFF-APRIL System
in B Cells in Health 255
1.4 The Role of the BAFF-APRIL System
on B Cells in Disease 257
The Lymphotoxin Pathway: Shaping B
Cell Environments 261
2.1 Introduction 261
2.2 Receptors and Ligands of the LT
Pathway 261
2.3 The Role of B Cell-Associated LTa^2
in Immune Cell Homeostasis 263
2.4 The Role of B Cell-Associated
LTctißz and the GC Reaction 264
2.5 LT and Mucosal B Cell Biology 265
2.6 LT and Tertiary Lymphoid
Structures 267
2.7 LT—Therapeutic Perspectives that
Pertain to B Cells 268
Conclusions and Perspectives 269
References 269
16. The Mucosal Immune System: Host-
Bacteria Interaction and Regulation of
Immunoglobulin A Synthesis
Sidonia Fagarasan, Giuliana Magri and
Andrea Cerutti
1. Introduction 2 77
2. Geography, Regulation, and Properties
of Gut Immunoglobulin A 277
3. Synthesis of Gut Immunoglobulin A 278
4. T Cell-Dependent Immunoglobulin A
Induction 278
4.1 Germinal Center Reaction 279
xii Contents
5.
4.2 Regulation of Germinal Centers
4.3 Specific Characteristics of Gut
Germinal Centers
T Cell-Independent Immunoglobulin A
Induction
5.1
6.
7.
8.
Immunoglobulin A Generation
in Isolated Lymphoid Follicles
Immunoglobulin A Generation in
Mesenteric Lymph Nodes and Peyer s
Patches
Immunoglobulin A Generation in
the Intestinal Lamina Propria
Function of Immunoglobulin A
Clinical Relevance
Conclusions
References
5.2
5.3
17. Cut Microbiota and Their
Regulation
Frederick W. Alt and Duane R. Wesemann
18. Molecular Mechanisms of AID
Function
Nasim A. Begum, Fiitoshi Nagaoka,
Maki Kobayashi and Tasuku Flonjo
1.
2.
3.
Introduction
AID Structure and Function
2.1 General Structural Features and
Functional Associations of AID
2.2 Proteins That Interact with AID
AID s Molecular Mechanism of DNA
Cleavage and Recombination
3.1 Properties of AID-lnduced DNA
Cleavage
Evidence for AID s Cytidine
Deamination Activity on DNA
or RNA
Two Separate AID Functions
DNA Deamination Hypothesis
RNA Editing Hypothesis
The Mechanism of AID s Specificity
Determination for DNA Cleavage
4.1 Cleavage Target Sequence:
c/s Recognition and Transcription
3.2
3.3
3.4
3.5
281
281
282
282
283
283
285
285
286
286
305
306
306
308
312
312
317
317
317
318
320
320
4.3
4.4
6.
4.2 The DNA Deamination Model
Requires AID-Targeting Cofactors 322
Target Chromatin: Accessibility and
Specificity 323
Chromatin Regulators for AID-lnduced
Cleavage and Repair 325
Regulation of AID Expression 328
5.1 AID s Expression Profile 328
5.2 Aicda Regulation 329
5.3 Post-Transcriptional and
Post-Translational AID Regulation 331
Concluding Remarks 331
References 332
1. Microbiota 293
2. Microbes, Primary Ig Diversification, 3.
and Early Life B Cell Selection 294 4.
3. Microbial Influence on IgA Production 297
4. Microbial Influence on IgE Production 299 5.
5. B-Lineage Cell Influence on Commensal
Microbes 300 6.
6. Conclusion 302
References 302
19. The Mechanism of IgH Class
Switch Recombination
Fei-Long Meng, Frederick W. Alt and Ming Tian
1. Antibody Class 345
2. Organization of Mouse IgH Locus 345
2.1 Activation-Induced Cytidine
Deaminase, SHM, and IgH GSR 345
A Two-Step Model of CSR 347
Mechanisms by Which AID Initiates
CSR and SHM 347
Germline S Region Transcription Targets
AID Activity during CSR 348
Role of Transcription Stalling in AID
Targeting 349
6.1 S Region Functions in CSR 349
7. AID Cofactors Facilitate AID Access
to Its ssDNA Substrates 350
8. Differential AID Targeting and
Outcomes during CSR and SHM 350
9. Long-Range Joining of S Region Breaks 351
10. Classical Nonhomologous End Joining 352
11. Alternative End Joining 353
11.1 ATM-Dependent DNA Repair
Response 354
12. Chromosomal Translocation in Lymphomas
Caused by Aberrant CSR 354
13. Evolution of the IgH CSR Mechanism 355
Acknowledgments 356
References 356
20. Somatic Hypermutation: The
Molecular Mechanisms
Underlying the Production
of Effective High-Affinity
Antibodies
Alberto Martin, Richard Chahwan,
Jahan Yar Parsa and Matthew D. Scharff
1. Introduction
363
Contents
XIII
2.
4.
5.
6.
1.1 Somatic Hypermutation
1.2 Gene Conversion
1.3 Class Switch Recombination
Activation-Induced Cytidine Deaminase
in Somatic Hypermutation
2.1 Substrate Specificity of AID
2.2 Sequence Specificity of AID-lnduced
Mutations
2.3 Catalytic Mechanism for AID
Targeting of the SHM
3.1 The Role of Transcription in AID
Deamination
3.2 Histone Modifications and AID
Accessibility
3.3 Nucleosomal Remodeling, AID
Accessibility, and Somatic
Hypermutation
3.4 Cis-Acting Elements in Somatic
Hypermutation
3.5 Trans-Acting Factors in Targeting
Somatic Hypermutation
Activation-Induced Cytidine Deaminase
and Downstream Repair Pathways
Mismatch Repair in Somatic Hypermutation
5.1 Detecting dU:G Mismatch at V-Regions
by MMR
5.2 Mismatch Repair Signaling during
SHM
5.3 Resolution of the dU:dG Mismatch
and Generation of dA:dT Mutations
5.4 Human Mutations in MMR Factors
and Their Effect on SHM
Base Excision Repair in Somatic
Hypermutation
363
364
365
365
365
367
367
368
368
369
6.1 Detection of the dU:dG Mismatch at
V-Regions by BER
6.2 Signaling BER at the Ig Locus
6.3 Resolution of the dU:dG Mismatch via
BER
6.4 Human Mutations in BER Factors and
369
369
370
371
373
374
377
377
378
378
378
379
379
4.1 Transcriptional Regulation of AID 390
4.2 Posttranscriptional Regulation
of AID 390
5. Aberrant AID Expression by Pathogen
Infection and Tumorigenesis 391
5.1 Aberrant AID Expression in
Hematopoietic Cells 391
5.2 Aberrant AID Expression in
Epithelial Cells 391
6. Conclusion 393
References 394
22. Molecular Pathogenesis of
B Cell Lymphomas
Riccardo Dalla-Favera and Laura Pasqualucci
1.
2.
Introduction 399
The Cell of Origin of Lymphomas 399
2.1 BCLs and the Germinal Center
Reaction 399
Mechanisms of Genetic Lesion in
Lymphoma 401
3.1 Chromosomal Translocations 401
3.2 Copy Number Gains and
Amplifications 401
3.3 Gain-of-Function Mutations 402
3.4 Inactivating Mutations and
Deletions 402
3.5 Aberrant SHM 402
3.6 Infectious Agents 402
Molecular Pathogenesis of Most
Common Lymphoma Types 403
4.1 Mantle Cell Lymphoma 403
4.2 Burkitt Lymphoma 403
4.3 Follicular Lymphoma 404
4.4 Diffuse Large B Cell Lymphoma 405
4.5 Chronic Lymphocytic Leukemia 408
4.6 Hodgkin Lymphoma 408
References 409
Their Effect on SHM 6.5 Crosstalk between MMR and 379 23. B Cells Producing Pathogenic Autoantibodies
BER during SHM 380
7. Conclusion 380 Yong-Rui Zou and Betty Diamond
References 380 1. Origin of Autoantibodies 1.1 B1 Cells and Natural 417
. Aberrant AID Expression by Autoantibodies 417
Pathogen Infection 1.2 B2 Cells and Pathogenic
Atsushi Takai, Hiroyuki Marusawa and Tsutomu Chiba Autoantibodies 1.3 Mechanisms that Breach B Cell 420
1. Introduction 389 Tolerance 420
2. Physiologic Role of Activation-Induced 2. Immunodeficiency, B Cell Malignancy,
Cytidine Deaminase 389 and Auto reactivity 425
3. AID Induction in B Cells 390 2.1 Immunodeficiency 425
4. Regulation of AID Expression in B Cells 390 2.2 B Cell Malignancy 426
xiv
Contents
3. Features of Pathogenic
Autoantibodies
3.1 Pathogenicity of Autoantibodies
3.2 Structural Basis of Autoreactivity
4. Effector Mechanisms of Pathogenic
Autoantibodies
4.1 Noninflammatory Autoimmune
Disorders Mediated by Autoantibodies
4.2 Inflammatory Autoimmune Disorders
Mediated by Autoantibodies
5. B Cells as the Therapeutic Target in
Autoimmune Disease
6. Conclusion
References
24. The Cellular and Molecular
Biology of HIV-1 Broadly
Neutralizing Antibodies
Barton F. Haynes, Kevin O. Saunders, Garnett
Kelsoe, John R. Mascola and Gary J. Nabel
1. Introduction
2. Highly Conserved Structures on
HIV-1 Env
3. Mechanisms of HIV-1 Neutralization by
Antibodies
4. Role of Neutralizing Antibodies in
Protection from HIV-1 Transmission
5. Biology of Broad Neutralizing Antibody
Development
6. Characteristics of HIV-1 Env Neutralizing
Antibodies
6.1 VRC01 -Class of CD4 Binding Site
bnAbs
6.2 V1V2 and Other Glycan-Targeted
bnAbs
6.3 CD4bs Loop Binding bnAbs
6.4 Env gp41 bnAbs
7. HIV-1 Env Antibodies Induced by Current
HIV Vaccine Candidates
8. New Strategies for Induction of HIV-1
bnAbs
8.1 B Cell Lineage Immunogen Design
8.2 Envelope Scaffolds
8.3 Envelope Multi mers
8.4 Minimal Immunogens
8.5 Soluble gp140 Trimers
9. Summary
References
25. Immune Deficiencies Caused
by B Cell Defects
Anne Durandy, Sven Kracker and Alain Fischer
1. Defects in B Cell Development 464
1.1 Defects in Pre-BCR Expression or
Signaling 464
1.2 Defects in B and Other Lineages
Development 465
2. Defects in B Cell Migration 467
3. Defects in B Cell Survival 468
4. Defects in B Cell Activation 470
4.1 Defects in BCR Costimulatory
Molecules and BCR Signaling 470
4.2 Defects in T and B Cell Activation 470
4.3 Defects in the NF-kB Pathway 471
4.4 Defects in Ig Class Switch
Recombination 471
4.5 Defects in Cytokine Signaling 473
5. PADs with Unknown Etiology 474
5.1 Common Variable Immunodeficiency 474
5.2 Selective Ig Deficiency 474
6. Therapeutic Approaches 475
7. Conclusion 475
References 475
26. IMGT® Immunoglobulin
Repertoire Analysis and Antibody
Humanization
Marie-Paule Lefranc
1. IMGT® and the Birth of Immunoinformatics 481
2. Fundamental Information from
IMGT-ONTOLOGY Concepts 482
2.1 Identification: IMGT® Standardized
Keywords 482
2.2 Description: IMGT® Standardized
Labels 482
2.3 Classification: IMGT® Standardized
Genes and Alleles 483
2.4 Numerotation: IMGT Unique Numbering
and IMGT Collier de Perles 484
3. IMGT® Immunoglobulin Repertoire
Analysis 490
3.1 IMGTA/-QUEST 490
3.2 IMGT/H igh V-QU EST 496
4. IMGT® Antibody Engineering and
Humanization 501
4.1 IMGT/DomainGapAlign 501
4.2 IMGT/3Dstructure-DB 502
4.3 IMGT/2 Dstructure-DB 507
4.4 IMGT® V and C Domain Annotation
for Antibody Humanization,
Engineering, and Evolution 507
5. Conclusion 510
6. Availability and Citation 511
Acknowledgment 511
References 511
426
426
427
428
428
429
431
433
433
441
442
443
446
446
449
449
449
450
450
452
453
453
453
454
454
455
455
455
Contents
xv
27. Anti-interleukin-6 Receptor
Antibody Therapy Against Autoimmune
Inflammatory Diseases
Toshio Tanaka, Masashi Narazaki and Tadamitsu
Kishimoto
1. lnterleukin-6 and Its Receptor System
2. Pleiotropic Activity of IL-6
2.1 Activity on Hepatocytes
2.2 Activity in the Innate and Acquired
Immune Systems
2.3 Activity in Other Cells
3. Regulation of IL-6 Synthesis
4. Dysregulated Persistent IL-6 Synthesis
has a Pathologic Role in the Development
of Various Diseases
5. A Humanized Anti-IL-6 Receptor Antibody
for Treatment of Autoimmune Inflammatory
Diseases
6. lnterleukin-6 Blockade Affects B- and
T-Cell Function In Vivo; Lessons from
Tocilizumab Treatment
7. Concluding Remarks
8. Conflict of Interest
References
28. Targeting the IL-17/IL-23 Axis
in Chronic Inflammatory
Immune-Mediated Diseases
Alexander Tsoukas, Carl S. Goodyear and
lain B. Mclnnes
1. Introduction
2. The IL-17 Family
3. IL-17 Receptor/Pathway
3.1 Type 17 T Cells
4. Th17 Cell Differentiation
515
516
516
516
518
518
519
520
5. Cellular Sources and Targets 529
6. The Role of the IL-17/23 axis in
Immune-mediated Inflammatory Diseases 530
6.1 Rheumatoid Arthritis 530
7. Crohn s Disease 531
7.1 Clinical Trials 531
8. Psoriasis 532
8.1 Clinical Trials 532
9. Psoriatic Arthritis 534
9.1 Trials 534
10. Ankylosing Spondylitis 535
10.1 Clinical Trials 536
10.2 Other Conditions 536
10.3 Adverse Effects/Safety/Potential Risks 536
11. Summary 536
References 537
29. Discovery and Development
of Anti-TNF Therapy: Pillar of a
Therapeutic Revolution
521 Marc Feldmann
521 1. Introduction 541
522 2. How was TNF Defined as a Therapeutic
522 Target? 541
3. Establishing the Clinical Utility of Anti-TNF
Therapy 543
4. Proof of Efficacy 544
5. Optimizing Long-term Use 544
6. Phase III Clinical Trials 544
7. Conclusions 544
Acknowledgments 545
527 References 545
527
528
528
529 Index 549
|
| any_adam_object | 1 |
| author2 | Alt, Frederick W. |
| author2_role | edt |
| author2_variant | f w a fw fwa |
| author_facet | Alt, Frederick W. |
| building | Verbundindex |
| bvnumber | BV042133080 |
| classification_rvk | WF 9880 |
| ctrlnum | (OCoLC)915668514 (DE-599)BVBBV042133080 |
| discipline | Biologie |
| edition | 2. ed. |
| format | Book |
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| id | DE-604.BV042133080 |
| illustrated | Illustrated |
| indexdate | 2024-07-10T01:13:30Z |
| institution | BVB |
| isbn | 9780123979339 |
| language | English |
| oai_aleph_id | oai:aleph.bib-bvb.de:BVB01-027573203 |
| oclc_num | 915668514 |
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| owner | DE-188 DE-11 DE-29T |
| owner_facet | DE-188 DE-11 DE-29T |
| physical | XXII, 563 S. Ill., graph. Darst. |
| publishDate | 2015 |
| publishDateSearch | 2015 |
| publishDateSort | 2015 |
| publisher | Elsevier [u.a.] |
| record_format | marc |
| spelling | Molecular biology of B cells ed. by Frederick W. Alt ... 2. ed. Amsterdam [u.a.] Elsevier [u.a.] 2015 XXII, 563 S. Ill., graph. Darst. txt rdacontent n rdamedia nc rdacarrier Molekularbiologie (DE-588)4039983-7 gnd rswk-swf B-Zelle (DE-588)4147096-5 gnd rswk-swf B-Lymphozyt (DE-588)4137121-5 gnd rswk-swf Molekularbiologe (DE-588)1023071983 gnd rswk-swf B-Lymphozyt (DE-588)4137121-5 s Molekularbiologe (DE-588)1023071983 s DE-604 B-Zelle (DE-588)4147096-5 s Molekularbiologie (DE-588)4039983-7 s 1\p DE-604 2\p DE-604 Alt, Frederick W. edt HBZ Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=027573203&sequence=000002&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis 1\p cgwrk 20201028 DE-101 https://d-nb.info/provenance/plan#cgwrk 2\p cgwrk 20201028 DE-101 https://d-nb.info/provenance/plan#cgwrk |
| spellingShingle | Molecular biology of B cells Molekularbiologie (DE-588)4039983-7 gnd B-Zelle (DE-588)4147096-5 gnd B-Lymphozyt (DE-588)4137121-5 gnd Molekularbiologe (DE-588)1023071983 gnd |
| subject_GND | (DE-588)4039983-7 (DE-588)4147096-5 (DE-588)4137121-5 (DE-588)1023071983 |
| title | Molecular biology of B cells |
| title_auth | Molecular biology of B cells |
| title_exact_search | Molecular biology of B cells |
| title_full | Molecular biology of B cells ed. by Frederick W. Alt ... |
| title_fullStr | Molecular biology of B cells ed. by Frederick W. Alt ... |
| title_full_unstemmed | Molecular biology of B cells ed. by Frederick W. Alt ... |
| title_short | Molecular biology of B cells |
| title_sort | molecular biology of b cells |
| topic | Molekularbiologie (DE-588)4039983-7 gnd B-Zelle (DE-588)4147096-5 gnd B-Lymphozyt (DE-588)4137121-5 gnd Molekularbiologe (DE-588)1023071983 gnd |
| topic_facet | Molekularbiologie B-Zelle B-Lymphozyt Molekularbiologe |
| url | http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=027573203&sequence=000002&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
| work_keys_str_mv | AT altfrederickw molecularbiologyofbcells |