The Variation and Adaptive Expression of Antibodies

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Harvard University Press, 1973 - Science - 219 pages
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During the past ten years, several theories have been proposed on the origin of the diversity of antibodies. George P. Smith presents a critical study of these theories in this detailed treatment of immunological problems from the point of view of molecular genetics.

Mr. Smith uses a new and simplifying approach to this long-standing controversy. By a comprehensive computerized analysis of antibody amino acid sequences (particularly the myeloma proteins), the author traces their evolution and matches his results against the expectations of the various theories of diversity. He discusses at length the other types of evidence as well.

Mr. Smith also deals with the clonal specialization of cells to produce a single antibody, and the relationship of this specialization to the somatic joining of antibody half-genes, which is one of the immune system's most important peculiarities.

Introductory material is provided to make this work understandable to molecular geneticists not versed in immunology and to immunologists not versed in molecular genetics.

This is a timely book offering a succinct and coherent summary of the various lines of evidence in a confused and controversial field.

 

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Contents

Introduction to the Immune Response
1
Tables and Figures
2
The Number of Antibodies
9
Figure 14 Number of antibodies inferred from sequence comparisons
10
Table 21 Nomenclature for immunoglobulins
17
Table 23B C sequences
24
Table 25 Cregion subclasses
31
Reconstructing Protein Evolution
38
Figure 614 Evolution of VH method of minimum mutations
102
The Meaning of Sequence Identities
107
Figure 616 Hypothetical structure of DNARNA hybrid
112
Evidence
113
Table 71 Evidence for subgroups in rabbit V genes
118
The Clonal Selection Theory
127
Figure 81 Minimum elements of a theory of selective antibody
128
Table 81 Specialization of cells at the antibodyproduction stage
134

Figure 31 Computation of minimum mutations
40
The Method of Fitch and Margoliash
45
Figure 33 Reconstruction by the method of Fitch and Margoliash
47
Evolution
51
Figure 41 Survey of Cregion evolution method of Fitch
54
Figure 43 Summary of Cregion evolution
60
Theories of Antibody Diversity
62
The Somatic Recombination Theory
73
Figure 61 Expectations of the somatic mutation theory
76
Figure 64 Detection of recombination by genealogical methods
83
The Evolution of VK Regions
84
Figure 68 Evolution of human VKj regions method of minimum
89
The Evolution of V Regions
94
Figure 611 V evolution positions 1 to 20 method of Fitch
95
The Evolution of VH Regions
100
Recommitment of Cells from IgM to IgG
142
Table 83 Wellestablished human germline genes
146
Theories of Joining and Commitment
151
Figure 94 DNA network model
154
Programmed Gene Translocations and Differentiation
158
Appendix A Properties and Provenances of Immunoglobulin
165
properties and references
172
Appendix B Immunoglobulin Allotypes
174
Table B2 Rabbit allotypes
178
Table B6 Variation in C regions
184
The Ribosomal RNA Genes
187
References
195
Index
217
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