Elsevier S & T

Molecular Biology of B Cells

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Table of contents
  • Contributorsv
  • Contentsvii
  • Prefacexiii
  • 1 Human Immunoglobulin Heavy Chain Locus1
  • Organization of the Human VH Locus2
  • Analysis of Human VH Segments7
  • Evolution of the Human VH Locus10
  • Human CH Locus12
  • 2 Immunoglobulin Heavy Chain Genes of Mouse19
  • Igh-V or VH Genes of the Ighb Haplotype19
  • Polymorphism in VH Genes21
  • Evolution24
  • Genomic Considerations24
  • 3 Immunoglobulin K Genes of Human and Mouse27
  • General Features of Human and Mouse K Genes27
  • Human Immunoglobulin K Genes27
  • Mouse Immunoglobulin K Genes30
  • Aspects of Evolution of the K Genes33
  • 4 Immunoglobulin Lambda (IGL) Genes of Human and Mouse37
  • IGL Genes and IMGT-ONCOLOGY37
  • The Human IGL Genes40
  • The Mouse IGL Genes50
  • 5 The Mechanism of V(D)J Recombination61
  • Antigen Receptor Gene Assembly62
  • Mutational Analyses of Recombination Signal Sequences64
  • Beyond 12/23Ž Restriction of V(D)J Rearrangements64
  • Influence of Coding Flanks65
  • The Biochemistry of V(D)J Cleavage65
  • RAG1/2-RSS Binding66
  • RAAG1/2 Post-Cleavage Complex67
  • A Role for HMG1 (or HMG2) in V(D)J Recombination67
  • A Closer Look at RAAG1 and RAG268
  • Colding and Signal Joint Formation Requires the NHEJ Pathway71
  • 6. Transcription of Immunoglobulin Genes83
  • Transcriptional Regulatory Elements in Immunoglobulin Heavy and Light Chain Genes83
  • Proteins Binding in Ig Transcriptional Regulatory Elements86
  • Areas of Current Research89
  • Discoveries Resulting from the Study of Ig Gene Transcription93
  • 7. Early B Cell Development to a Mature, Antigen-Sensitive Cell101
  • Three Waves of Hematopoiesis During Embryonic Development101
  • Pluripotent Hematopoietic Stem Cells103
  • Pathways of Hematopoietic Progenitor Cells Toward B Lymphocyte Lineage Commitment and Differentiatio106
  • Control of Lymphoid Cell Development by Transcription Factors107
  • Plasticity if PAX-5–Deficient Pre-B Cells109
  • The Surrogate Light Chain110
  • Pre-B Cells and Their Differentiation to More Mature B Lineage Cells112
  • Rearrangements at the L Chain Loci at the Transition from Large to Small Pre-B-II Cells114
  • Immature B Cells116
  • Selections of Immature B Cells117
  • 8. Allelic Exclusion, Isotypic Exclusion, and the Developmental Regulation of V(D)J Recombination127
  • Rag Expression127
  • The 12/23 Rule128
  • Accessibility Hypothesis128
  • Enhancer and Promoter Control of V(D)J Recombination128
  • Trans-Acting Factors130
  • Chromatin Dynamics and V(D)J Recombination130
  • Ordered Rearrangement Within Ig and TCR Loci132
  • Allelic Exclusion at Ig and TCR Loci133
  • Ig Light Chain Isotypic Exclusion136
  • Future Directions136
  • 9. The Development of Human B Lymphocytes141
  • Stages of Human B Cell Differentiation141
  • Sites of Human B Cell Development143
  • Human Immunoglobulin Genes143
  • The Role of Surrogate Light Chains in Human B Cell Development144
  • Repertoire Diversification via Receptor Editing and VH Replacement145
  • Regulation of Antibody Production by B Cell Receptors147
  • Immunodeficiency Diseases148
  • B Lineage Leukemia149
  • 10. Development and Function of B Cell Subsets155
  • Selection and Differential Survival Mechanisms„B Cell Receptor Signaling156
  • Compartmentalization of B Cell Subsets157
  • Other Factors Involved in Formation of B Cell Subsets157
  • 11 Structure and Function of B Cell Antigen Receptor Complexes161
  • Structure of the BCR Complex161
  • Coupling Between the BCR and SYK162
  • Redox Regulation of BCR Signaling162
  • ITAM- and Non-ITAM-Controlled Signaling Pathways to SLP-65163
  • ITAM-Independent Signaling and Fine-Tuning165
  • 12. Regulation of Antigen Receptor Signaling by the Co-Receptors, CD19 and CD22171
  • CD19171
  • Inhibitory Co-Receptors on B Cells177
  • 13 The Dynamic Structure of Antibody Responses187
  • Three Routes to Antibody Production187
  • Stages of Adaptive Antibody Responses187
  • How and Where B Cells Encounter Antigen188
  • Primary Cognate Interaction of B Cells with Primed T Cells189
  • Exponential Growth of Activated B Cells190
  • Proliferation, Hypermutation, and Selection in GC192
  • Sustained Survival of Memory B Cell Clones and Plasma Cells197
  • 14 Dynamics of B Cell Migration to and within Secondary Lymphoid Organs203
  • Lymphoid Organ Entry203
  • Compartmentalization of Mature B Cells209
  • B Cells at Sites of Inflammation213
  • Homing of Antibody Secreting Cells (ACSs)213
  • 15 Characteristics of Mucosal B Cells with Emphasis on the Human Secretory Immune System223
  • Immune-Inductive Tissue Compartments223
  • Characteristics of B Cells in Secretory Effector Tissues226
  • B-Cell Stimulation in MALT Structures229
  • Class Switch and Ig A Isotype Promotion232
  • Mechanisms Directing Homing and Retention of Mucosal B Cells234
  • What Is Actually Known About Human Mucosal B Cells?238
  • 16 The Cellular Basis of B Cell Memory247
  • Generation of B Cell memory and Memory B Cells in T Cell-Dependent Antibody Responses247
  • Memory Plasma Cells252
  • Adaptive B Cell Memory254
  • 17 Immunoglobulin Assembly and Secretion261
  • Mechanisms of IG Synthesis and Assembly261
  • Multiple Layers of Quality Control Exist to Aid and Monitor the Assembly of Functional IGs264
  • Transport of Assembled IG Molecules to the Golgi267
  • Degradation of Misfolded and Unassembled IG Subunits267
  • Differentiation to Plasma Cell268
  • 18 Fc and Complement Receptors275
  • Consequences of FC RIIB Deficiency275
  • Consequences of Complement and Complement Receptor Deficiencies276
  • Fc Receptors276
  • Complement Receptors280
  • Co-Receptor Signaling Versus Antigen Localization to FDC281
  • Frontiers: Complement Versus Fc Receptors285
  • 19 Regulation of Class Switch Recombination289
  • CSR Requires Specific Stimuli Occurring in a Defined Germinal Center (GC) Microenvironment289
  • Proximal CIS Regulatory Elements for GT290
  • Distant Regulatory Region for GT and CSR: The 3'IGH Enhancers294
  • Mechanisms for 3'IGH Regulatory Region-Mediated Regulation of GT296
  • Coordinated Regulation of Transcription, Recombination, and Replication300
  • 20 Molecular Mechanism of Class Switch Recombination307
  • Outline of Mechanisms for CSR307
  • Isotype Specificity of CSR312
  • AID, The Sole B Cell-Specific Factor Required for CSR313
  • Cleavage of the S Region314
  • Processing and Joining of DNA Ends After Cleavage315
  • Comparison of CSR with SHM319
  • 21 Molecular Mechanism of Hypermutation327
  • Characteristics of Somatic Hypermutation of Immunoglobulin Variable Regions327
  • Activation and Targeting of Hypermutation by Transcription and CIS-Elements329
  • Hypermutation Occurs Within a Limited Window of B Cell development330
  • The AID Gene Is Critical for Hypermutation331
  • Phase One of Hypermutation: C &arrow; U Deamination and Base Excision Repair332
  • Mismatch Repair Factors in Phase Two of Hypermutation332
  • DNA Breaks in Hypermutation334
  • Competing Pathways of Repair: Error-Prone DNA Synthesis or Strand Transfer335
  • Evolution and Hypermutation335
  • 22 Selection During Antigen-Driven B Cell Immune Responses: The Basis for High Affinity Antibody339
  • Overview of the B-Cell Immune Response339
  • Affinity Maturation in the Early Stages of the B-Cell Immune Response341
  • The CG Is a Second Major Site for Affinity Maturation342
  • Affinity-Based Selection Continues After the GC Reaction Has Ended344
  • An Integrated View of the Strategic Design of the B-Cell Immune Response: Future Directions344
  • 23 Chromosomal Translocations in B-Cell Leukemias and Lymphomas A.349
  • Translocations Associated with a Block in Lymphoid Differentiation349
  • Translocations Associated with Suppression of Apoptosis During Lymphoid Development352
  • Translocations Associated with Increased Proliferation in Lymphoid Precursors354
  • Activation Cell Cycle Regulation in Mantle Cell Lymphoma and Myeloma355
  • 24 Classification and Characteristics of Mouse B Cell–Lineage Lymphomas365
  • Comparative Classification of Mouse and Human B Cell–Lineage Neoplasms366
  • Characteristics of Mouse B Cell–Lineage Lymphomas368
  • Pathogenesis373
  • 25 B Cells Producing Pathogenic Autoantibodies381
  • Subsets of Autoantibodies382
  • Criteria to Define Pathogenic Autoantibodies383
  • Genetics of Autoantibodies384
  • Molecular and Immunochemical Characteristics of Human Pathogenic Autoantibodies388
  • Human Pathogenic Autoantibodies with Murine Counterparts392
  • 26 Immunodeficiencies Caused by B-Cell Defects403
  • Clinical Features of the Agammaglobulinemias403
  • Autosomal Recessive Hyper-IGM Syndrome410
  • Murine Models of Human B-Cell Deficiency412
  • 27 Diverse Forms of Immunoglobulin Genes in Lower Vertebrates417
  • Cartilaginous Fish: An Unusual Example of Gene Multiplicity417
  • Bony Fish: IG Heavy Chain Genes Resemble IgM and IgD419
  • Lobe-Finned Fish: A TransitionalŽ Arrangement of Recombining Elements422
  • Fleshy-Finned Fish: An Ancient Origin for Isotype Diversity422
  • Amphibians and Reptiles: The Possible Origins of Class Switching422
  • Light Chain Genes: Diverse Structures and Organization in Lower Vertebrates423
  • Transcriptional Control of IG Genes in Lower Vertebrates425
  • A Unifying Hypothesis to Explain the Origins of the Adaptive Immune Receptor427
  • Immune Molecules in Jawless Vertebrates427
  • Protochordates: Different Contexts for Diversified B Regions428
  • 28 Immunoglobulin Genes and Generation of Antibody Repertoires in Higher Vertebrates: A Key Role for433
  • Avians433
  • Lagomorphs436
  • Artiodactyls440
  • Other Mammals444
  • 29 The Zebrafish Immune System449
  • Hematopoiesis450
  • Adaptive Immunity in Zebrafish: Organs and Molecules452
  • Genetic Approaches457
  • Major Histocompatibility Complex (MHC)460
  • Innate Immunity460
  • Infection464
  • 30 The Origin of V(D)J Diversification473
  • The Alien Seed473
  • The Evolution of BCR and TCR Loci481
  • Considerations on the UR-V Gene483
  • 31 Antibody Structure and Recognition of Antigen491
  • A Structural Framework for Molecular Recognition491
  • 32 Monoclonal Antibodies from Display Libraries511
  • Overview of Antibody Phage Display513
  • Prokaryotic Expression of Antibody Fragments514
  • Generation of Antibody Gene Repertoires Using the Polymerase Chain Reaction515
  • Antibody Phage Display516
  • Use of Phage Display to Bypass Hybridoma Technology519
  • Use of Phage Display to Bypass Immunization520
  • A Comparison of Different Phage Antibody Library Types and Applications521
  • Strategies for Selection of Phage Antibodies522
  • Increasing Antibody Affinity Using Phage Display522
  • Alternative Antibody Display Technologies524
  • 33 Humanization of Monoclonal Antibodies533
  • Murine, Chimeric, and Humanized Antibodies533
  • Computer-Guided Design of Humanized V Regions534
  • Other Humanization Methods537
  • Immunogenicity of Humanized Antibodies540
  • Humanized Antibodies Approved for Clinical Use540
  • 34 Human Monoclonal Antibodies from Translocus Mice547
  • Human IG Transloci547
  • The Mouse Strains552
  • Index563
Book details
  • Vendor Elsevier S & T
  • SKU 9780120536412
  • ISBN-13 9780080479507

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Molecular Biology of B Cells is a comprehensive reference to how B cells are generated, selected, activated and engaged in antibody production. All these developmental and stimulatory processes are described in molecular and genetic terms to give a clear understanding of complex phenotyes. The molecular basis of many diseases due to B cell abnormality is also discussed. This definitive reference is directed at research level immunologists, molecular biologists and geneticists.