In recent years there have been major developments in the understanding of the mechanisms of action of immunoglobulins and natural antibodies, and in the pathogenesis of a number of neurological diseases. Furthermore, there has been a renewed interest in one of the oldest cytokines, the migration inhibition factor (MIF), for its role in inflammation and cancer. These were among the topics discussed at the second International Forum on Immunoglobulin Research (IFIR) held in Barcelona, Spain, on September 14– 17, 2011. Both IFIR and this supplement were sponsored by Baxter Healthcare Corporation. Immunoglobulins have both anti-inflammatory and proinflammatory effector properties that have been shown for both IgA and IgG isotypes. These contrasting properties make them attractive tools for the development of therapeutic approaches. Falk Nimmerjahn (Erlangen, Germany) discussed the use of animal model systems in understanding the mechanisms of IgG activities, and highlighted the differences in IgG subclasses and FcR between humans and even closely related monkeys. Because these differences limit extrapolation of data from monkeys to humans, he discussed various alternative animal model systems to study the mechanisms and limitations of therapeutic antibodies. These models include transgenic mice expressing human proteins regulated by their endogenous promoters. Immunodeficient mice like Rag2, SCID, or NOD/SCID are injected with human peripheral blood mononuclear cells, followed by injection of therapeutic antibodies. Another model, which appears to be the most desirable, transplants immunodeficient mice with human hematopoietic stem cells. Francis William Rogers Brambell, an Irish zoology professor, observed that passive transfer of immunity via gamma globulin occurred from mother to offspring, and subsequently hypothesized the existence of a receptor that can mediate the transfer of maternal gamma globulin to infant as well as the protection of gamma globulin from catabolism. Neil Simister and Keith Mostov purified and sequenced an Fc receptor from the intestine of an 11-day-old rat. The receptor, hence named neonatal FcR, was associated with β2-microglobulin, which is structurally similar to the MHC I molecule. In 1994, Pam Bjorkman and colleagues reported on the crystal structure of FcRn. FcRn is evolutionarily distinct from other FcRs and is expressed on a variety of tissues and cells. Richard Blumberg (Boston, MA, USA) discussed expression and functions of FcRn in adults at the level of the vascular endothelium, where it protects IgG from catabolism. Also, antigen-presenting cells use FcRn to recycle internalized IgG rather than destroy it. At the cell surface, FcγIIR would bind immune complexes; once internalized, immune complexes could be transferred to FcRn in the endosome and then returned to the cell surface, where they would be released at physiological pH for cross-presentation. Dr Blumberg also discussed engineering FcRn to increase binding of FcRn to IgG, which may be exploited for therapeutic purposes. Naive CD4 T cells differentiate into IL-17–producing Th17 cells, in which RORγt (RORC) transcription factor plays a critical role. IL-17 plays an important role in protecting against extracellular microbes, especially fungi. However, increased IL-17 is associated with inflammation and autoimmunity. Jagadeesh Bayry (Paris, France) discussed the effect of intravenous immunoglobulin (IVIG), which could be more appropriately termed immunoglobulin G S. Gupta (*) Division of Basic and Clinical Immunology, University of California, Irvine, CA, USA e-mail: sgupta@uci.edu
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Jun 1, 2013
J.P Powers + 11
Open Access