Beschreibung
The Antibody Enigma is a somewhat personal view of the antibody diversity question from two investigators who have spent the past 18 years trying to penetrate the enigma. It is not and was not meant to be an all-embracing comprehensively referenced review of the subject of antibody diversity. Because of the subjective viewpoint, there are un doubtedly omissions of data that others consider to be seminal, and if we have offended anyone by omitting their own contribution we sin cerelyapologize. We have lived with "The Enigma" on and off for the past two years. It has been both hard work and good fun but, above all, it has been a learning experience. There were several difficult decisions to make in putting together the final text, but perhaps the most difficult was de ciding upon a stopping point. The field of antibody diversity is presently enjoying an unparalleled expansion of information, and because of this it was very tempting to await further developments in hopes of tying up as many loose ends as possible. This was decided against for several reasons; the major factor was that the project was growing burdensome for both of us. From a more objective point of view this appears to be a reasonable time to stop our exposition.
Autorenportrait
Inhaltsangabe1. The Nature of the Problem.- 1.1. Introduction.- 1.2. Antibody Synthesis.- 1.3. Historical Roots.- 1.3.1. Introduction of the Germline Concept of Immunologic Specificity.- 1.3.2. Introduction of the Somatic Concept of Immunologic Specificity.- 1.4. Clonal Selection.- 1.5. Effector Functions.- >1.6. The Extent of Diversity-The Problem in a Nutshell.- 1.7. Scope of the Book.- 1.8. Precis.- References and Bibliography.- 2. The Serologist's Approach to the Problem.- 2.1. Introduction.- 2.2. Rabbit Allotypes.- 2.2.1. Discovery.- 2.2.2. Variable-Region Allotypes.- 2.3. Human Allotypes.- 2.3.1. Discovery.- 2.3.2. Allotypes and Isotypes.- 2.3.3. Haplogroups.- 2.4. Allotypes of the Mouse and the Rat.- 2.4.1. Mouse Allotypes.- 2.4.2. Allotypes of the Rat.- 2.5. Individual Antigenic Specificity and Idiotypy.- 2.5.1. Idiotypes of Human Immunoglobulins.- 2.5.2. Idiotypes of Rabbit Antibodies.- 2.5.3. Presence of Idiotypes on IgG and IgM.- 2.5.4. Idiotype versus IAS.- 2.6. Idiotypes as Markers for Antibody-Binding Regions.- 2.6.1. Idiotypic Cross-Specificity.- 2.6.2. Antigen Inhibition of Idiotype Reactions.- 2.6.3. Exceptions to the Correlation of Idiotypy and Binding Site.- 2.7. The Inheritance of Idiotypes.- 2.7.1. Discovery.- 2.7.2. The Mouse Idiotype Systems.- 2.8. Conclusion.- References and Bibliography.- 3. The Biochemist's Approach to the Problem.- 3.1. Biochemical Studies on Heterogeneous Antibodies.- 3.2. Biochemical Studies on Homogeneous Antibodies.- 3.2.1. Human Myeloma.- 3.2.2. Mouse Myeloma.- 3.2.3. Other Homogeneous Antibodies.- 3.2.4. Hybridomas.- 3.3. Structural Features of Immunoglobulin Isotypes and Allotypes.- 3.3.1. The Human Immunoglobulin Classes.- 3.3.2. The Carbohydrate Structures of Human Immunoglobulins.- 3.3.3. Comparisons of Immunoglobulins from Different Species.- 3.3.4. Immunoglobulin Allotypes.- 3.4. Structural Features of V Regions.- 3.4.1. V-Region Subgroups.- 3.4.2. Framework and Hypervariable Regions.- 3.4.3. The Antibody-Combining Site.- 3.5. Are the C Regions Really Constant?.- 3.6. Structural Analysis of Selected V Regions.- 3.6.1. Mouse V?.- 3.6.2. Mouse V?21.- 3.6.3. The Mouse V Ars Kappa Chains.- 3.7. Precis.- References and Bibliography.- 4. Unique Features of the Antibody Problem.- 4.1. Introduction.- 4.2. Structural Variability of Antibodies.- 4.2.1. Immunoglobulins and Major Histocompatibility Complex Proteins.- 4.2.2. Immunoglobulins and Hemoglobin.- 4.3. Two Genes-One Polypeptide Chain.- 4.3.1. The Todd Phenomenon.- 4.3.2. Structural Differentiation of V and C Regions.- 4.3.3. Statement of the Two-Gene Hypothesis.- 4.3.4. Cis or Trans Synthesis.- 4.3.5. Genetic Recombination between V- and C-Region Allotypes.- 4.3.6. Biclonal Myeloma Proteins.- 4.3.7. Cross-overs between Idiotypes and C Regions.- 4.3.8. Theoretical Impact of the Two-Gene Hypothesis.- 4.4. Allelic Exclusion.- 4.4.1. The Lyon Hypothesis.- 4.4.2. Selective Expression of Immunoglobulin Alleles.- 4.5. The Three Loci for Immunoglobulins.- 4.5.1. Kappa versus Lambda Light Chains.- 4.5.2. Expression of V-Region Subgroups.- 4.5.3. Allelic Selection of Immunoglobulin Genes.- 4.6. Conclusion.- References and Bibliography.- 5. The Polar Solutions.- 5.1. Introduction.- 5.2. The Germline Theory.- 5.3. The Somatic Mutation Theory.- 5.4. Data Favoring Germline Theories.- 5.4.1. V-Region Subgroups.- 5.4.2. Evolutionary Divergence (Trees).- 5.4.3. Inheritance of Idiotypes.- 5.5. Data Favoring Somatic Mutation Models.- 5.5.1. Phylogenetically Associated Residues.- 5.5.2. Mouse Lambda Light Chains.- 5.5.3. Rabbit Group a Allotypes.- 5.5.4. A V-Region Allotype for the Mouse Kappa Chain.- 5.6. Waiting for the Answer.- References and Bibliography.- 6. The Maverick Solutions.- 6.1. Introduction.- 6.2. Data Difficult to Rationalize with Either Germline or Somatic Theories.- 6.2.1. V-Region Subgroup Distinctions Are Not Evident throughout the V Regions.- 6.2.2. The Rabbit Allotypes Are Not Evident throughout the V Regions.- 6.2.3. Phylogenetically
