This book focuses on the function of antibodies in vivo. Recent years have seen an exponential
growth in knowledge about the molecular and cellular mechanisms of antibody activity. These new
results dramatically changed our view of how antibodies function in vivo. The importance of
this class of molecules is demonstrated by the heightened susceptibility to infections of
humans and mice with an altered capacity to generate pathogen specific antibody responses. Thus
the majority of our currently available vaccines such as vaccines against influenza measles
and hepatitis focus on the generation of long lasting antibody responses. Recent evidence from
a variety of in vivo model systems and from human patient cohorts has highlighted the exclusive
role of cellular Fc-receptors for certain immunoglobulin isotypes and subclasses. With the
recent discovery of a human Fc-receptor for IgM all different human immunoglobulin isotypes now
have a cellular receptor providing a feedback mechanism and link between antibodies and the
cellular components of the immune system. Moreover it has become clear the complement and
Fc-receptor system are tightly connected and regulate each other to ensure a well balanced
immune response. Among the immunoglobulin isotypes IgG plays a very important protective role
against microbial infections and also as a therapeutic agent to kill tumor cells or
autoantibody producing B cells in autoimmune disease. Transfer of our knowledge about the
crucial function of Fc-receptors has led to the production of a second generation of
therapeutic antibodies with enhanced binding to this class of receptors. Binding of antibodies
to Fc-receptors leads to the recruitment of the potent pro-inflammatory effector functions of
cells from the innate immune system. Hence Fc-receptors link the innate and adaptive immune
system emphasizing the importance of both arms of the immune system and their crosstalk during
anti-microbial immune responses. Besides this pro-inflammatory activity immunoglobulin G (IgG)
molecules are long known to also have an anti-inflammatory function. This is demonstrated by
the use of high dose intravenous immunoglobulins as a therapeutic agent in many human
autoimmune diseases. During the past five years several new insights into the molecular and
cellular pathways of this anti-inflammatory activity were gained radically changing our view of
IgG function in vivo. Several lines of evidence suggest that the sugar moiety attached to the
IgG molecule is responsible for these opposing activities and may be seen as a molecular switch
enabling the immune system to change IgG function from a pro- to an anti-inflammatory activity.
There is convincing evidence in mice and humans that aberrant IgG glycosylation could be an
important new pathway for understanding the impaired antibody activity during autoimmune
disease. Besides this tremendous increase in basic knowledge about factors influencing
immunoglobulin activity the book will also provide insights into how these new insights might
help to generate novel therapeutic approaches to enhance IgG activity for tumor therapy on the
one hand and how to block the self-destructive activity of IgG autoantibodies during
autoimmune disease on the other hand.
