1;Preface;5 2;List of Contents;7 3;List of Contributors;9 4;B Cell Tolerance-How to Make It and How to Break It;10 4.1;1 Introduction;11 4.2;2 Repertoire Selections by the pre-B Cell Receptor;15 4.3;3 Generation of Immature, sIgM+ B Cells;16 4.4;4 Negative and Positive Selection, and Ignorance of the Developing Immature B Cell Repertoires;18 4.5;5 Negative Selection and Editing;19 4.6;6 Ignorance;21 4.7;7 Positive Selection;22 4.8;8 Peripheral B CellsWithout sIg Expression;23 4.9;9 Rescue of Autoreactive B Cells by T Cell-Independent Antigens of Type I, TLR- Ligand- Antigen- Complexes;24 4.10;10 Autoreaction Rescued by Ignorance;25 4.11;11 Breaking the Tolerance ofMature, Peripheral B Cell Repertoires;26 4.12;12 Consequences of Breaking B Cell Tolerance-Autoimmune Diseases;28 4.13;References;29 5;Breaking Ignorance: The Case of the Brain;34 5.1;1 Introduction;35 5.2;2 Brain Autoantigens in the Immune System;36 5.3;3 B Cell Ignorance?;39 5.4;4 Activation of Ignorant Autoreactive T Cells- The Transition from Autoreactive to Autoaggressive;41 5.5;5 Regulatory Suppression of Autoimmune T Cells- But How Do Suppressor T Cells Know?;47 5.6;6 Conclusion;53 5.7;References;54 6;Naturally Arising Foxp3-Expressing CD25+ CD4+ Regulatory T Cells in Self- Tolerance and Autoimmune Disease;60 6.1;1 Introduction;61 6.2;2 Self-Tolerance Maintained by Thymus-Produced Natural Treg: Induction of Autoimmune Disease by Their Manipulation at the Cellular and Molecular Level;62 6.3;3 IPEX as an Example of Human Autoimmune Disease Due to a Genetic Defect of Naturally Arising CD25+ CD4+ Treg: Its Implications for Immunologic Self- Tolerance and Autoimmune Disease in Humans;66 6.4;4 Contribution of Impaired Immunoregulation and Host Genetic Factors to the Development of Autoimmune Disease: A Possible Mechanism of Autoimmune Disease;67 6.5;5 Conclusion and Perspective;71 6.6;References;71 7;Sex Hormones and SLE: Influencing the Fate of Autoreactive B Cells;76 7.1;1 Introduction;77 7.2;2 Estrogen, Prolactin, and B Cell Fate in the R4A Model;83 7.3;3 Clinical Relevance;88 7.4;4 Conclusion;89 7.5;References;90 8;Innate (Over)immunity and Adaptive Autoimmune Disease;98 8.1;1 Introduction;98 8.2;2 Autoimmunity and/or Infection;99 8.3;3 Innate Regulators of Autoreactive T Cell Priming;102 8.4;4 Regulatory T Cells and Their Relation to Toll-Like Receptor Signals;104 8.5;5 Lack of (Auto)immunity After Innate Overactivation: A Role for Interferons and the Nervous System;105 8.6;6 Autoreactivity and Conversion to Autoimmune Disease;106 8.7;7 Conclusion;108 8.8;References;109 9;Can Unresolved Infection Precipitate Autoimmune Disease?;114 9.1;1 Introduction;115 9.2;2 Crohn's Disease;116 9.3;3 Ankylosing Spondylitis and the Other Spondyloarthritides;121 9.4;4 Regulatory Mechanisms in Autoimmunity;124 9.5;References;127 10;The Systemic Autoinflammatory Diseases: Inborn Errors of the Innate Immune System;136 10.1;1 Introduction;137 10.2;2 Familial Mediterranean Fever;139 10.3;3 Syndrome of Pyogenic Arthritis, Pyoderma Gangrenosum, and Acne;142 10.4;4 The Cryopyrinopathies: Familial Cold Autoinflammatory Syndrome, Muckle- Wells Syndrome, and Neonatal- Onset Multisystem Inflammatory Disease;144 10.5;5 Blau Syndrome;148 10.6;6 TNF Receptor-Associated Periodic Syndrome;150 10.7;7 Hyperimmunoglobulinemia D with Periodic Fever Syndrome;154 10.8;8 Concluding Remarks;157 10.9;References;158 11;Inefficient Clearance of Dying Cells and Autoreactivity;170 11.1;1 The Comeback of Dying Cells;171 11.2;2 Various Molecules Are Involved in the Clearance of Dying Cells;172 11.3;3 C-Reactive Protein and Dying Cells;173 11.4;4 Complement and DNase I Act as Back-up Molecules in the Clearance Process;174 11.5;5 Phosphatidylserine Exposure as One Early Membrane Change of Apoptotic Cells;174 11.6;6 Changes in the Glycoprotein Composition of Membranes of Apoptotic Cells;175 11.7;7 Impaired Clearance Functions and Autoimmunity;177 11.8;8 Heterogeneous and Intrinsic Clearance Defects in Some SLE P