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IgE enhances specific antibody and T cell responses in mice overexpressing CD23
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
2007 (English)In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 66, no 2-3, 261-270 p.Article in journal (Refereed) Published
Abstract [en]

IgE administered with its specific antigen in vivo induces enhanced proliferation of specific T cells as well as enhanced production of specific antibodies. Both effects are dependent on the low-affinity receptor for IgE (CD23) and the underlying mechanism is thought to be increased antigen presentation following uptake of IgE/antigen complexes via CD23+ B cells. By contrast, CD23 negatively regulates antibody responses to antigens administered with alum, i.e. without IgE. This effect has been observed as low IgG1 and IgE responses in transgenic mice overexpressing CD23 (CD23Tg). The present study was designed to test whether IgE could enhance antibody and T-cell responses in CD23Tg animals or whether CD23's downregulatory effect precludes IgE-mediated enhancement. IgE-anti-TNP administered with OVA-TNP enhances the OVA-specific antibody responses in wild-type (wt) and CD23Tg mice equally well. Interestingly, the total magnitude of antibody responses to IgE + OVA-TNP and to uncomplexed OVA-TNP, as well as to sheep erythrocytes and keyhole limpet haemocyanine, were lower in the CD23Tg mice. IgE induced proliferation of OVA-specific CD4+ T cells to the same degree in wt and CD23Tg mice. The effect on T cells was dependent on CD23+ B cells as demonstrated in in vitro proliferation assays. In conclusion, CD23 does indeed have dual immunoregulatory effects in the same animal. The receptor mediates enhancement of antibody and T-cell responses to IgE-complexed antigen, most likely via increased presentation of complexed antigen, while it negatively regulates the total antibody response to a variety of antigens.

Place, publisher, year, edition, pages
2007. Vol. 66, no 2-3, 261-270 p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-95523DOI: 10.1111/j.1365-3083.2007.01953.xISI: 000248504100019PubMedID: 17635803OAI: oai:DiVA.org:uu-95523DiVA: diva2:169776
Available from: 2007-03-08 Created: 2007-03-08 Last updated: 2017-12-14Bibliographically approved
In thesis
1. Antibody Feedback Regulation and T Cells
Open this publication in new window or tab >>Antibody Feedback Regulation and T Cells
2007 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Antibodies, passively administered or actively produced, regulate immune responses to the antigen they recognize. This phenomenon is called antibody-mediated feedback regulation. Feedback regulation can be positive or negative, resulting in >1000-fold enhancement or >99% suppression of the specific antibody response. The outcome depends on size, structure, dose, and route of administration of the antigen as well as on class and subclass of the regulating antibody. This thesis investigates the role of T cells in antibody-mediated feedback enhancement, using both in vivo and in vitro approaches. IgE-antibodies enhance antibody responses to small soluble proteins. This effect is entirely dependent on the low-affinity receptor for IgE, CD23, and most likely depends on increased antigen presentation by CD23+ B cells. Strengthening this hypothesis, we show that IgE-mediated CD4+ T cell proliferation in vitro required the presence of CD19+ CD43- CD23+ B cells. CD23 has also been shown to negatively regulate immune responses. Transgenic mice overexpressing CD23 are known to have impaired responses to antigens in alum. We here demonstrate that they are normal regarding IgE-mediated enhancement. IgG3 enhances antibody responses, and previous data suggested involvement of complement. We found that IgG3-mediated enhancement works well in mice lacking the only Fc-receptor known to bind IgG3, CD64. Although IgG3 could enhance antibody responses it had no major effect on T cell responses. Complement-receptors 1/2 (CR1/2) are required for the initiation of normal antibody responses. Although mice lacking CR1/2 had impaired antibody responses after immunization with sheep erythrocytes, their specific T cell responses were unaffected. The presented data do not support the idea that increased complement-mediated antigen presentation is a major mechanism behind the involvement of complement in antibody responses. They support the hypothesis that antigens forming complement-containing immune complexes may activate specific B cells by co-crosslinking BCR and CR1/2.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2007. 46 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 233
Keyword
Fc receptors, B cell, T cell, antigen presentation, complement receptors, complement, IgE, IgG3, CD23, antibody
National Category
Immunology in the medical area
Identifiers
urn:nbn:se:uu:diva-7631 (URN)978-91-554-6814-9 (ISBN)
Public defence
2007-03-30, Rudbecksalen, Rudbecklaboratoriet, Dag Hammarskölds väg 20, Uppsala, 09:15
Opponent
Supervisors
Available from: 2007-03-08 Created: 2007-03-08Bibliographically approved

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Heyman, Birgitta

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