Description
A series of volumes devoted to molecular immunology will contain, for the most part, articles which attempt to explain immunological phenomena in terms of the behavior and properties of particular molecules. Many of the articles in this volume do this. At the same time, there are many instances-and this is particularly so in the case of immunology-where phenomena must first be described and interpreted in terms of the properties and behavior of cells. Most of us would hope that in due course a fuller understanding will be forthcoming. This volume starts off with such a contribution. Perhaps the most fascinat ing problem in immunology is how diversity is generated. There are two broad proposals: (1) that complete information exists ab initio (the germ-line theory), and (2) that there is initially a limited amount of information, and diversity is generated by somatic mutation. The issue is unresolved, but Cunningham has taken many of the data which have previously been used to support the germ-line theory and shows that the interpretations are not always clear-cut and can frequently be used to support another possibility-that new specificities may arise after stimulation of appropriate cells by antigens. And he has produced experimental evidence to support this notion. On the other hand, there can be little doubt that to a considerable degree the specificity of the immune response is determined by the selection by antigen of cells with receptors of appropriate specificity. This is essentially a surface phenomenon. The Generation of Antibody Diversity: Its Dependence on Antigenic Stimulation.- I. Introduction.- II. Explanation of the Theory.- III. Changes in the Patterns of Antibody Produced during the Course of an Immune Response.- A. Affinity.- B. Lag Phase.- C. Specificity.- IV. Numbers of B Cells.- V. Studies on Single Clones.- A. Isoelectric Focusing.- B. Lymph Node Fragment Cultures.- VI. Genetic Control of Antibody Production.- VII. Self-Tolerance.- VIII. Experimental Approaches.- IX. Discussion.- X. Summary.- Acknowledgments.- References.- Preparation and Properties of Lymphocyte Plasma Membrane.- I. Introduction.- II. Isolation of Plasma Membrane.- A. Source of Lymphocytes.- B. Disruption of Lymphocytes.- C. Subcellular Fractionation.- III. Properties of Plasma Membrane.- A. Purity.- B. Composition.- IV. Summary.- Acknowledgment.- References.- Immunogenicity In Vitro: Structural Correlation.- I. Introduction.- II. Direct Stimulation of B Cells.- A. Thymus Independence.- B. Macrophage Independence.- C. Correlation of Macrophage and Thymus Independence.- III. Structure-Activity Relationships.- A. Antigens.- B. Mitogens.- IV. A Special Example of Thymus-Independent Antigens – Antigen Bound to Macrophages via IgT.- V. Can Nonpolymeric Antigens Induce B-Cell Responses?.- VI. Relationship of B-Cell Differentiation to Induction.- VII. Relationship of Epitope Density to the Induction of Immunity and Tolerance.- VIII. Discussion.- A. How do Polymers with Repeating Determinants Stimulate B Cells?.- B. Discrimination Between Immunization and Tolerance Induction of B Cells.- IX. Abbreviations.- References.- mRNA for H and L Chains of Immunoglobulin: Specific Control of H-Chain Production.- I. Introduction.- II. L-Chain mRNA.- III. H-Chain mRNA.- IV. Nuclear Precursor of H-Chain mRNA.- V. Translational Control of H-Chain Synthesis.- VI. Specificity and Nature of H2L2 Interaction with H-Chain mRNA.- VII. Concluding Remarks.- References.- The J Chain of Polymeric Immunoglobulins.- I. Introduction.- II. Class Distribution.- III. Species Distribution.- IV. Detection of J Chain.- V. Isolation of J Chain.- A. Electrophoretic Methods.- B. Ion-Exchange Chromotography.- C. Other Methods.- VI. Physical-Chemical Properties.- A. Partial Specific Volume.- B. Molecular Weight.- C. Shape.- VII. Chemical Composition.- VIII. Stoichiometry.- IX. Site of J-Chain Attachment.- X. The Requirement for J Chain by IgM Molecules.- XI. Cellular Origin of J Chain.- XII. The Assembly of Polymeric Immunoglobulins.- A. Assembly of IgA.- B. Assembly of IgM.- Acknowledgment.- References.- Phylogenetic Aspects of Immunoglobulin Variable Region Diversity.- I. Introduction.- II. Variable Region Subgroups.- A. Definition.- B. Distribution of Variable Region Subgroups among Various Species.- C. Limitations on Sequence Variability in the V Region.- D. Phylogenetically Associated (Species-Specific) Residues within Immunoglobulin Polypeptide Chains.- E. Summary and Conclusions.- Acknowledgments.- References.- Separation Methods for Lymphocyte Populations.- I. Introduction.- II. Preliminary Steps: Preparation of Clean Cell Suspensions.- A. Preparation of Single Cell Suspensions from Solid Tissue.- B. Removal of Damaged Cells.- C. Elimination of Erythrocytes.- D. Elimination of Erythrocytes and Isolation of Lymphocytes from Blood.- III. Separation Based on the Physical Parameters of Cells.- A. Sedimentation-Velocity Separation.- B. Density Separation.- C. Electrophoretic Separation.- D. Counter-Current Distribution in Aqueous Polymer Two-Phase Systems.- IV. Adherence Separation of Lymphocytes and Phagocytes.- A. Active-Adherence Separation of Phagocytes from Lymphocytes.- B. Physical Adherence Column Separation between Lymphocyte Subpopulations.- V. Separation Based on Specific Cell Surface Receptors and Antigens.- A. Affinity-Column and Fiber Fractionation.- B. Specific Modification of Physical Properties.- C. Cytotoxic Antisera and Damaged Cell Removal.- VI. Electronic Cell Sorting.- References.- Radioelectrocomplexing: A General Radioimmunoassay Procedure for the Detection of Primary Binding of Antigen by Antibody.- I. Introduction.- II. Materials and Methods.- A. Antigens.- B. Antisera.- C. Radioelectrocomplexing.- D. Equilibrium Dialysis.- III. Quantitative Studies.- A. DNP/anti-DNP.- B. HSA/anti-HSA.- IV. Applications of Radioelectrocomplexing.- A. Alpha-Fetoprotein.- B. Hepatitis B Antibody.- C. Hepatitis B Antigen.- V. Summary and Conclusions.- Acknowledgments.- References.
