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Fcγ Receptors in th...
Fcγ Receptors in the Immune Response
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- Díaz de Ståhl, Teresita, 1961- (author)
- Uppsala universitet,Institutionen för genetik och patologi
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- van de Winkel, Jan, Professor (opponent)
- Department of Immunology, University Medical Center, KC.02-085.2 Utrecht
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(creator_code:org_t)
- ISBN 9155451756
- Uppsala : Acta Universitatis Upsaliensis, 2001
- English 58 s.
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Series: Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, 0282-7476 ; 1102
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Abstract
Subject headings
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
Keyword
- Genetics
- Fc Receptors
- IgG Receptors
- IgE Receptors
- Immune regulation
- In vivo animal models
- Mouse
- Rh prophylaxis
- Rheumatoid arthritis
- Transgenic/knockout
- Genetik
- Clinical genetics
- Klinisk genetik
- Pathology
- patologi
Publication and Content Type
- vet (subject category)
- dok (subject category)
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