Naturally Occurring Antibodies (NAbs)

285 Pages·2012·3.12 MB·English

by  Christoph J. Binder (auth.)

Naturally Occurring Antibodies (NAbs)
ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY
Editorial Board:
NATHAN BACK, State University of New York at Buffalo
IRUN R. COHEN, The Weizmann Institute of Science
ABEL LAJTHA, N.S. Kline Institute for Psychiatric Research
JOHN D. LAMBRIS, University of Pennsylvania
RODOLFO PAOLETTI, University of Milan
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Volume 750
NATURALLY OCCURRING ANTIBODIES (NAbs)
Hans U. Lutz
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Naturally Occurring Antibodies
(NAbs)
Edited by
Hans U. Lutz
Institute of Biochemistry, Swiss Federal Institute of Technology, ETH Hönggerberg
Zurich, Switzerland
Springer Science+Business Media, LLC
Landes Bioscience
Springer Science+Business Media, LLC
Landes Bioscience
Copyright ©2012 Landes Bioscience and Springer Science+Business Media, LLC
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Naturally Occurring Antibodies (NAbs), edited by Hans U. Lutz. Landes Bioscience / Springer Science+Business
Media, LLC dual imprint / Springer series: Advances in Experimental Medicine and Biology.
ISBN 978-1-4614-3460-3 ISBN 978-1-4614-3461-0 (eBook)
DOI 10.1007/978-1-4614-3461-0
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Library of Congress Cataloging-in-Publication Data
Naturally occurring antibodies (NAbs) / edited by Hans U. Lutz.
p. ; cm. -- (Advances in experimental medicine and biology ; v. 750)
Includes bibliographical references and index.
ISBN 978-1-4614-3460-3
I. Lutz, Hans U., 1942- II. Series: Advances in experimental medicine and biology ; v. 750. 0065-2598
[DNLM: 1. Antibodies--immunology. W1 AD559 v.750 2012 / QW 575]
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616.07’98--dc23
2012005554
DEDICATION
Dedicated to my wife, Ivanka Lutz, for supporting my efforts in editing this book
v
PREFACE
Welcome to a subject that is new for some and barely understood by others: naturally
occurring antibodies. The term “naturally occurring (auto)antibodies” (NAbs) stands for
physiological antibodies, or autoantibodies generated in healthy humans and/or vertebrates,
in contrast to those that are induced by exogenous antigens. In the years passed, some
authors in the field used instead the term “natural (auto)antibodies”. Though “induced” and
“naturally occurring” antibodies differ in many aspects from each other, both are “natural”
in the sense that they are produced by nature. Therefore, other authors have coined the
term “(auto)antibodies produced constitutively”, implying that such (auto)antibodies are
produced without stimulation by exogenous antigen molecules. For simplicity, we use
here the term “naturally occurring (auto)antibodies”, abbreviated as NAbs.
The existence of NAbs in healthy beings contrasted with the immunologic dogma,
formulated in 1959 by Burnet, according to whom “auto-reactive cell clones do not exist
in healthy beings, because they are deleted in ontogeny.” During the next 30 years or so, a
few hundred scientists in different countries nevertheless dared to continue to investigate
NAbs and their unique properties, so to say in the backyard of immunology. These scientists
learned that upon investigation NAbs have close to germline immunoglobulin chain
sequences and their production does not require induction by exogenous antigens. It is
certain that NAbs have developed over millions of years. NAbs are produced spontaneously
and some can be upregulated by the presence of autoantigens (rather than induced).
In order to give the reader an idea of the fascinating potential of NAbs, this volume
illustrates first the functional properties of NAbs. Authors from pioneering groups
report in their chapters on the tissue homeostatic, tissue regenerating and regulatory
properties of NAbs and NAbs in pooled human IgG (Chapters 1-4, 6-7 discuss these
findings). They found for the first time that many NAbs are involved in the clearance
of senescent, apoptotic and oxidatively damaged cells, as well as tumor cells. Another
group of researchers (Chapter 5) has been interested in how NAbs exert their effects and
has found that some NAbs gain functionality not only by binding to their antigens but by
modifying bound antigens enzymatically. Others (Chapter 8) discovered NAbs that have
a protective effect against viral and bacterial infections (first line defense), or that have
a disease-inhibiting potential in so far uncurable diseases, as it is emerging for multiple
sclerosis and Alzheimer’s disease (Chapters 4 and 7).
vii
viii PREFACE
Scientists interested in the regulation and modulation of components of the immune
system found a whole variety of NAbs to cytokines with regulatory and protective
functions and NAbs that modulate, e.g., dendritic cells, regulatory T cells, B cells and
granulocytes (Chapters 9-12). Two chapters (13,14) report that NAbs with beneficial roles
can become initiators of disease following the destruction of biological compartments or
following proteolytic modification of NAbs.
Thorough studies of the unique properties of NAbs (Chapters 15-17) have increased
our understanding of their stepwise generation in ontogeny and the phenomenon of
polyspecificity. Many studies on NAbs have been carried out on pooled human IgG
and later on IVIG (immunoglobulin for intravenous application) prepared from human
IgG. Considering the large plasma pools and initial difficulties in preparing IVIG that
does not induce adverse effects upon infusion into recipients, this volume ends with a
historical chapter on how pooled human plasma was fractionated and the IgG component
pretreated for a safe intravenous application (Chapter 18). The first positive effects of
immunoglobulin molecules in IVIG were observed in 1981 in treating patients with an
iatrogenic IgG deficiency and secondary ITP. This result called for similar IVIG treatments
of other autoimmune diseases, as reported later in numerous publications. The clinical
success combined with the low adverse event profile of IVIG therapies stimulated the
interest in NAbs, the potential mediators of the beneficial effects of IVIG.
My thanks go to the contributing authors for the effort and enthusiasm they have
devoted to their subject and to this task. Along with my coauthors we thank Landes
Bioscience for having offered the opportunity to compose this work and provide the first
open platform on NAbs. We hope to have triggered your interest.
Hans U. Lutz
Zurich, Switzerland
ABOUT THE EDITOR...
HANS U. LUTZ, born May 5, 1942 is a Swiss citizen. He completed his studies
in microbiology and biochemistry with a PhD at the University of Zurich in 1971 and
received “summa cum laude” for the exam and his dissertation on photophosphorylation
in chromatophores of Rhodospirillum rubrum in the group of Prof. R. Bachofen. During
his postdoctoral period he got familiar with the characterization of artificial membranes
(Prof. P. Läuger, University of Konstanze, Germany) and with membrane biochemistry at
the Worcester Foundation for Experimental Biology, Shrewsbury, USA, in collaborating
with Prof. J. Palek and G. Fairbanks. His interest in red blood cell (RBC) membrane
biochemistry was the basis for the discovery that ATP-depletion of RBC results in
the release of hemoglobin-filled vesicles that lack the cytoskeleton. In returning to
Switzerland in 1976 he joined the Institute of Biochemistry at the Swiss Federal Institute
of Technology (ETH), where he eventually had a tenure position until his retirement, some
teaching duties in biochemistry and immunology (complement), for some years extra
responsibilities in the research commission of the ETH, the European group for red cell
membrane research, the Board of the European complement network, and throughout the
time he had the freedom of an investigator to get grant money and bright PhD students.
He developed his own research field related to RBC aging. In the late 70s and early
80s he isolated and described the first IgG naturally occurring antibodies (NAbs) to red
blood cell membrane proteins (to spectrin and to band 3 protein) and presented evidence
for their role in tissue homeostasis. The low affinity IgG anti-band 3 NAbs directed to
the anion transport protein bind bivalently to oligomerized band 3 protein as generated
ix
during erythrocyte aging and oxidative damage. In trying to understand how such low
titer, low affinity NAbs can effectively opsonize erythrocytes, he found with his group that
immune-complexed anti-band 3 NAbs preferentially capture dimeric C3b because these
NAbs have a rare affinity for C3 within the Fab portion. Indeed, artificially generated
C3b-IgG complexes stimulated complement amplification 750 times better than C3b.
2
In extending these findings his group discovered that dimeric C3b deposits best to any
immune complex formed from F(ab’) because the lack of the Fc portion facilitates
2
deposition of dimeric C3b, but dimeric C3b deposits only if the F(ab’)-IC is rigidified
2
by bound IgG anti-hinge NAbs. Thus, anti-hinge NAbs that normally downregulate
antibody production by B cells (Terness et al) contribute to initiation of a systemic
inflammatory reaction when proteases released from neutrophils and pathogens (primarily
elastase) cleave IgG molecules into F(ab’) fragments. He could verify with his group
2
and clinicians that at the onset of a systemic inflammatory response in sepsis stimulation
of complement amplification (factor Bb) is proportional to F(ab’) production and both
2
parameters depend linearly on liberated elastase.
x