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Efficient IgG-mediated suppression of primary antibody responses in Fcgamma receptor-deficient mice
Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
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1999 In: Proc Natl Acad Sci U S A, Vol. 96, no 5, 2244-2249 p.Article in journal (Refereed) Published
Place, publisher, year, edition, pages
1999. Vol. 96, no 5, 2244-2249 p.
URN: urn:nbn:se:uu:diva-89553OAI: oai:DiVA.org:uu-89553DiVA: diva2:161134
Available from: 2001-11-23 Created: 2001-11-23Bibliographically approved
In thesis
1. Fcγ Receptors in the Immune Response
Open this publication in new window or tab >>Fcγ Receptors in the Immune Response
2001 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Circulating immune complexes play an important role in the modulation of antibody responses and in the pathogenesis of immune diseases. This thesis deals with the in vivo regulatory properties of antibodies and their specific Fc receptors.

The immunosuppressive function of IgG is used clinically, to prevent rhesus-negative women from becoming sensitized to rhesus-positive erythrocytes from the fetus. The mechanism behind this regulation is poorly understood but involvement of a receptor for IgG, FcγRII, has been suggested. It is shown in this thesis that IgG and also IgE induce immunosuppression against sheep erythrocytes to a similar extent both in mice lacking all the known Fc receptors as in wild-type animals. These findings imply that antibody-mediated suppression of humoral responses against particulate antigens is Fc-independent and that the major operating mechanism is masking of epitopes.

Immunization with soluble antigens in complex with specific IgG leads to an augmentation of antibody production. The cellular mechanism behind this control is examined here and it is found that the capture of IgG2a immune complexes by a bone marrow-derived cell expressing FcγRI (and FcγRIII) is essential. An analysis of the ability of IgG3 to mediate this regulation indicated that, in contrast, this subclass of IgG augments antibody responses independently of FcγRI (and FcγRIII). These findings suggest that distinct mechanisms mediate the enhancing effect of different subclasses of antibodies.

Finally, the contribution of FcγRIII was studied in the development of collagen-induced arthritis (CIA), an animal model for rheumatoid arthritis in humans. It was discovered that while DBA/1 wild-type control mice frequently developed severe CIA, with high incidence, FcγRIII-deficient mice were almost completely protected, indicating a crucial role for FcγRIII in CIA.

The results presented here help to understand how immune complexes regulate immune responses in vivo and show that Fc receptors for IgG, if involved, could be new targets for the treatment of immune complex-related disorders.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2001. 58 p.
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 0282-7476 ; 1102
Genetics, Fc Receptors, IgG Receptors, IgE Receptors, Immune regulation, In vivo animal models, Mouse, Rh prophylaxis, Rheumatoid arthritis, Transgenic/knockout, Genetik
National Category
Medical Genetics
Research subject
urn:nbn:se:uu:diva-1545 (URN)91-554-5175-6 (ISBN)
Public defence
2001-12-14, Rudbecksalen, Rudbeck Laboratory, Uppsala, 13:15
Available from: 2001-11-23 Created: 2001-11-23Bibliographically approved

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