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Antibody Feedback Regulation: From Epitope Masking to T Helper Cell Activation
Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
2004 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Antibodies have the ability to influence the antibody response against the very antigen they are specific for, in a process called antibody feedback regulation. Depending on the nature of the antigen, the antibody response can be either enhanced or almost completely inhibited. This thesis focuses on the underlying mechanisms of antibody feedback regulation in vivo.

Antigen-specific IgG can inhibit the antibody response to a particulate antigen. Based on its ability to inhibit B cell activation, the inhibitory FcγRIIB (low affinity receptor for IgG) has been suggested to be involved. Here we show that although FcγRIIB is required for efficient suppression in vitro, it is not required in vivo. Therefore, even though FcγRIIB can inhibit antibody responses, other mechanisms (such as epitope masking and enhanced antigen clearance) play a more dominant role in vivo.

The antibody response to soluble antigen is greatly enhanced when it is introduced to the immune system in complex with antigen-specific IgG or IgE. We found that FcγRIIB attenuates the magnitude of IgG-mediated enhancement. In mice lacking FcγRIIB, IgG enhanced the antibody response much more efficiently than in normal mice.

Since B cells require CD4+ T cell help in order to become antibody-producing cells, we examined the CD4+ T cell response to immune complexes in vivo. Using an adoptive transfer strategy with transgenic ovalbumin (OVA)-specific CD4+T cells, we could show that the enhanced OVA-specific IgG response to IgG2a/OVA and IgE/OVA complexes was preceded by a potent OVA-specific CD4+ T cell response. IgG2a-mediated enhancement was dependent on activating Fcγ receptors, whereas IgE-mediated enhancement was dependent on CD23, the low affinity receptor for IgE. We identified CD23+ B cells as the responsible effector cells for IgE-mediated enhancement in vivo. Taken together, these results show that Fc receptor-mediated antigen presentation is a major mechanism underlying antibody feedback enhancement.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis , 2004. , p. 53
Series
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 0282-7476 ; 1377
Keyword [en]
Immunology, Immune regulation, B cells, T cells, Antibodies, Fc Receptors, Antigen presentation, Transgenic/Knockout Mice
Keyword [sv]
Immunologi
National Category
Immunology in the medical area
Identifiers
URN: urn:nbn:se:uu:diva-4580ISBN: 91-554-6055-0 (print)OAI: oai:DiVA.org:uu-4580DiVA, id: diva2:165205
Public defence
2005-01-14, Rudbecksalen, Rudbeck Laboratory, Dag Hammerskjöldsväg 20, Uppsala, 09:15
Opponent
Supervisors
Available from: 2004-12-20 Created: 2004-12-20 Last updated: 2018-01-13Bibliographically approved
List of papers
1. FcγRIIB in IgG-mediated suppression of antibody responses: Different impact in vivo and in vitro
Open this publication in new window or tab >>FcγRIIB in IgG-mediated suppression of antibody responses: Different impact in vivo and in vitro
2001 (English)In: Journal of Immunology, Vol. 167, p. 5558-5564Article in journal (Refereed) Published
Identifiers
urn:nbn:se:uu:diva-92211 (URN)
Available from: 2004-12-20 Created: 2004-12-20 Last updated: 2011-06-28Bibliographically approved
2. IgG2a-mediated enhancement of antibody and T cell responses and its relation to inhibitory and activating Fcγ receptors
Open this publication in new window or tab >>IgG2a-mediated enhancement of antibody and T cell responses and its relation to inhibitory and activating Fcγ receptors
2004 (English)In: Journal of Immunology, Vol. 172, p. 5269-5276Article in journal (Refereed) Published
Identifiers
urn:nbn:se:uu:diva-92212 (URN)
Available from: 2004-12-20 Created: 2004-12-20 Last updated: 2011-06-28Bibliographically approved
3. IgE enhances antibody responses and T cell activation in vivo: A central role for B cells
Open this publication in new window or tab >>IgE enhances antibody responses and T cell activation in vivo: A central role for B cells
(English)Manuscript (Other academic)
Identifiers
urn:nbn:se:uu:diva-92213 (URN)
Available from: 2004-12-20 Created: 2004-12-20 Last updated: 2011-06-28Bibliographically approved

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