Table Of ContentBiological Applications
of
Anti-Idiotypes
Volume I
Editor
Constantin A. Bona, M.D., Ph.D.
Professor of Microbiology
Mount Sinai School of Medicine
New York, New York
CRC Press
Taylor & Francis Group
Boca Raton London New York
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First published 1988 by CRC Press
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Reissued 2018 by CRC Press
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Library of Congress Cataloging-in-Publication Data
Biological applications of anti-idiotypes.
Bibliography: p.
Includes indexes.
1. Immunoglobulin idiotypes. 1. Bona, Constantin A.
QR186.7.B565 1988 616.07’93 87-20833
ISBN 0-8493-6941-X (v. 1)
ISBN 0-8493-6942-8 (v. 2)
ISBN 0-8493-6940-1 (set)
A Library of Congress record exists under LC control number: 87020833
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PREFACE
The most demanding aspect of editing a book dealing with a specialized scientific topic
is covering a vast body of literature through which as much available information as possible
on the subject is obtained. However, it is also undeniable that much is gained from this
mandatory exercise, not only to have a deep insight into the intimate dialectic of a science
and the evolution of its concepts, but also the position which a particular discipline occupies
among the realm of the general sciences of nature is revealed.
Comparatively speaking, immunology is a young science. In contrast to many sciences
conceived 25 centuries ago under a Hellenistic sky dominated by the postulate that the
universe is governed by rules accessible to the human mind, immunology was born at the
end of the last century. In spite of its youth, the rapidity at which progress in the understanding
of a system was attained in immunology is rivaled in very few fields. Such an accomplishment
is attributable to the application of the same principles of creativity which permitted com-
parable achievements in other disciplines.
The strategy of immunological research was based on analysis: namely, the dissection of
the components of the immune system and synthesis of information into the formulation of
concepts. Often, investigators possessed sufficient insight and understanding of their systems
to allow them to cumulate concepts even before their analytical studies were completed.
Other elements have also contributed to the rapid progress in immunology. First, research
tactics were continuously adapted to take advantage of recent technological advances. There
is no doubt that the success of experimental work is directly related to the technological
approaches employed. Second was the collective character of the research. This is probably
related to the interdisciplinary character of the science. It is compulsory for an immunologist
to not only keep abreast of the technology but also to be familiar with the principles of
biology and medicine to understand the organization and function of the immune system
and the implication of any alteration of these functions in various diseases. Of course, it is
not possible to minimize the role which intuition plays in contributing to brilliant discoveries.
Intuition is an individual event which allows one to find the most suitable approach leading
to a major scientific breakthrough.
I do not believe that intuition is due to chance. Rather, it represents an excellent chron-
ological juxtaposition between the accumulation of a critical amount of analytical findings
and the erudite ability of conceptual synthesis culminating in a giant strike forward. Only
well-prepared persons can have such illuminating intuition.
The text of a scientific book requires a few basic elements which include the presentation
of findings, concepts, and theories. The presentation of findings is an essential component
of this type of publication when they are the fruit of correctly executed experiments that
can be assigned to the category of "eternal truths" which are no longer susceptible to
transformation or improvement. However, it should be recognized that there is a legion of
findings whose presentation is just a means to achieve a more distinct goal.
Indeed, one may ask whether a histologist who spent his life peering through a microscope
at slides made from a horse, in fact, knows how the horse looks or runs.
To study the lymphocyte (its structure and physiology), biosynthetic products, and genes
is not a goal in itself; such studies achieve a meaningful aim only by the collective integration
of all the knowledge which they provide into a coherent assembly. Newton perhaps provided
the best example of this in science by understanding that the physical laws governing the
fall of a stone also govern the movement of stars.
The presentation of concepts requires a keen selection process in order to retrieve from
the reams of available information these seminal findings supporting the concepts as well
as the exceptions. Two features should not be forgotten in this regard. First, concepts are
not everlasting since they are formulated from a limited amount of available information.
It is intriguing to follow the rapid transformation of concepts and models in immunology
as new findings are brought to light. The second is to place in the proper perspective the
anthropocentric input in concepts which are aimed at defining objective laws to rationalize
the phenomena. I feel that numerous concepts and models in immunology have too much
anthropomorphic input; sometimes we must resist the temptation to formulate orderly rules
for governing a system when our true mission is only to unravel them.
The third element is the presentation of theories, classifying the findings into categories
in a coherent order, and integrating the concepts. Theories are also not timeless since the
curiosity of the experimental investigator continuously generates new findings by challenging
the established theories. Thus, the writing of a scientific book is just a beginning and each
beginning is imperfect.
The goal of this book was to present findings which are supportive of the concept that
the words of the idiotype dictionary and likewise self-recognition are essential for com-
munication between lymphocyte clones while some unfaithful ("infidel") copies of the
words contained in the idiotype dictionary perhaps play a role in the functional regulation
of nonlymphoid cells.
The notion of self-recognition as a regulatory force was very important for my under-
standing of idiotype regulation. Since immunology evolved as a discipline of microbiology,
a major paradigm which dominated immunological theories was selection during phylogeny
of lymphocytes to ensure the defense mechanisms. Therefore, the immune system is oriented
solely towards the recognition of foreign antigens. We wanted to point out that idiotype
mediated self-recognition is an important regulatory force within the immune system.
THE EDITOR
C. A. Bona, M.D., Ph.D., is Professor of Microbiology at Mount Sinai School of
Medicine, New York.
Dr. Bona received his M.D. and Ph.D. degrees in Medical Science from the Faculty of
Medicine, Bucharest, and his Docteur in Sciences Naturelles degree from Paris University.
Dr. Bona has published more than 150 papers in various national and international journals,
29 chapters in various monographs, 6 sections in textbooks, has edited 2 monographs, and
has written 2 books on idiotypes.
His major research interest is in the idiotypy field in which he discovered the naturally
occurring idiotype-specific T cells, regulatory idiotopes, epibodies, and the first demon-
stration that an anti-Id antibody can elicit (instead of an antigen) an immune response against
a bacterial antigen. This observation stimulated the research in the utilization of idiotypes
as vaccines.
CONTRIBUTORS
Volume I
Clifford J. Bellone, Ph.D. Sylvie Corbet
Professor Centre d'Immunologie
Department of Microbiology Institut National de la Sante et de la
St. Louis University School of Medicine Recherche Medicale
St. Louis, Missouri Centre National de la Recherche
Scientifique
Kim Bottomly, Ph.D. Marseille, France
Associate Professor
Department of Pathology Frank W. Fitch, M.D., Ph.D.
Yale University Medical School Department of Pathology
New Haven, Connecticut and
The Ben May Institute
Christian Cambillau, Dr. es Sc. University of Chicago
Charge de Recherche Chicago, Illinois
Centre de Recherche sur les Mecanismes
de Croissance Cristalline Michel Fougereau, D.V.M., Dr Sci
Marseille, France Professor
Centre DTmmunologie
J.D. Capra, M.D. Institut National de la Sante et de la
Professor Recherche Medicale
Department of Microbiology Centre National de la Recherche
University of Texas Health Scientifique
Science Center at Dallas Marseille, France
Dallas, Texas
Sherman Fong, Ph.D.
Dennis A. Carson, M.D.
Assistant Member
Member
Basic and Clinical Research
Basic and Clinical Research
Scripps Clinic and Research Foundation
Scripps Clinic and Research Foundation
La Jolla, California
La Jolla, California
Sundararajan Jayaraman, Ph.D.
Pierre-Andre Cazenave, Ph.D.
Research Fellow
Professor
Unite dTmmunochimie Analytique Department of Pathology
Harvard Medical School
Institut Pasteur
Boston, Massachusetts
Paris, France
Pojen P. Chen, Ph.D. John F. Kearney
Assistant Member Professor
Basic and Clinical Research Department of Microbiology
Scripps Clinic and Research Foundation University of Alabama
La Jolla, California Birmingham, Alabama
Keith A. Knisley, Ph.D. Daniele Primi, Ph.D.
Postdoctoral Fellow Unite d'Immunochimie Analytique
Department of Pathology Institut Pasteur
University of Texas Medical School Paris, France
Houston, Texas
Gilbert Mazza, Dr. es Sc. Jose Rocca-Serra, Doctorat d'Etat
Charge de Recherche Maitre de Conference 1 ere Classe
Centre d'Immunologie Centre d'Immunologie
Institut National de la Sante et de la Institut National de la Sante et de la
Recherche Medicale Recherche Medicale
Centre National de la Recherche Centre National de la Recherche
Scientifique Scientifique
Marseille, France Marseille, France
Kathryn Meeke, D.V.M.
Research Assistant Professor
L. Scott Rodkey, Ph.D.
Department of Microbiology
Associate Professor
University of Texas Health
Department of Pathology
Science Center at Dallas
University of Texas Medical School
Dallas, Texas
Houston, Texas
Michele Milili, Dr. Universite
Technician
Centre d' Immunologie
Claude Roth
Institut National de la Sante et de la
Departement d'Immunologie
Recherche Medicale
Institut Pasteur
Centre National de la Recherche
Paris, France
Scientifique
Marseille, France
Claudine Schiff, Dr. es Sc.
Daniel Moinier, B.T.S.
Charge de Recherche
Technician
Centre d' Immunologie
Centre d'Immunologie
Institut National de la Sante et de la
Institut National de la Sante et de la
Recherche Medicale
Recherche Medicale
Centre National de la Recherche
Centre National de la Recherche
Scientifique
Scientifique
Marseille, France
Marseille, France
Philippe Oilier, M.D.
Centre d'Immunologie
Institut National de la Sante et de la Gerard Somme, Dr. es Sc.
Recherche Medicale Assistant
Centre National de la Recherche Departement d'Immunologie
Scientifique Institut Pasteur
Marseille, France Paris, France
J. Theze, Dr. es Sc. Meenal Vakil, Ph.D.
Chef d' Unite Research Scientist
Departement d'Immunologie Department of Microbiology
Institut Pasteur University of Alabama
Paris, France Birmingham, Alabama
Cecile Tonnelle, Dr. es Sc. Carol Victor-Kobrin, Ph.D.
Charge de Recherche Assistant Professor
Centre d'Immunologie Department of Microbiology
INSERM-CNRS Mount Sinai School of Medicine
Marseille, France New York, New York
TABLE OF CONTENTS
Volume I
Chapter 1
Anti-Idiotypes 1
C. Bona
Chapter 2
Structure and Genetics of AB2 13
K. Meek and J. D. Capra
Chapter 3
Molecular Basis of Anti-Idiotypes Antibodies Carrying Internal Image of Antigens 23
M. Fougereau, C. Cambillau, S. Corbet, G. Mazza, M. Milili, D. Moiner,
P. Oilier, J. Rocca-Serra, C. Roth, C. Schiff, G. Somme, J. Theze, and C. Tonnelle
Chapter 4
Molecular Basis of Epibody Reactivity 41
P. Chen, S. Fong, and D. Carson
Chapter 5
Monoclonal Antibodies Specific for VH and VK Isotypes as Probes for the Analysis of
the VH Repertoire 57
D. Primi and P.-A. Cazenave
Chapter 6
Expression of Idiotypes and Anti-Idiotypes During Development: Frequency and
Functional Significance in the Acquisition of the Adult Repertoire 75
M. Vakil and J. Kearney
Chapter 7
Auto-Anti-Idiotype Antibodies 91
K. Knisley
Chapter 8
Regulatory Function of Anti-Idiotype Autoantibodies 105
C. Victor-Kobrin
Chapter 9
Antibodies Specific for the T Cell Receptor 137
F. Fitch
Chapter 10
The Idiotypic Specific Repertoire is Determined by Idiotype Prevalence 153
K. Bottomly
Chapter 11
Idiotypic-Specific Suppressor T Cells 165
S. Jayaraman and C. Bellone
Index 189
