Feedback Enhancement of Immune Responses by IgE, IgM, and IgG3 Antibodies
2015 (English)Doctoral thesis, comprehensive summary (Other academic)
Antibodies can enhance or suppress the immune responses against their specific antigens. This phenomenon is known as antibody-mediated feedback regulation. We have studied the mechanisms underlying IgE-, IgM-, and IgG3-mediated enhancement of immune responses in mouse models using intravenous immunization. We attempted to answer the following questions: 1) Which cell type presents IgE-complexed antigens to CD4+ T cells? 2) Is complement activation required for specific IgM to enhance antibody responses? 3) Does IgM enhance CD4+ T-cell responses? 4) How are IgG3-antigen complexes transported into B-cell follicles?
We found that CD23+ B cells transporting IgE-antigen complexes into B-cell follicles were not required to prime the antigen-specific CD4+ T cells in vivo, whereas CD11c+ cells were indispensable. After examining the three most common subpopulations of CD11c+ cells in the spleen, we determined that it was CD8α- conventional dendritic cells migrating into the T-cell zone following immunization that presented IgE-complexed antigens to CD4+ T cells.
Next, we showed that specific IgM from Cµ13 mice, which is unable to activate complement, failed to enhance either antibody or germinal center responses whereas wild-type IgM enhanced both responses. Therefore, specific IgM must activate complement to enhance humoral responses. In addition, wild-type IgM did not up-regulate CD4+ T-cell responses.
Finally, we showed that IgG3-antigen complexes were transported by marginal zone B cells into B-cell follicles via binding to complement receptors 1 and 2 (CR1/2) on those cells. The immune complexes were captured by follicular dendritic cells as early as 2 h after immunization. Germinal center responses were also enhanced by IgG3. Using bone marrow chimeric mice, we found that CR1/2 expression was required on both marginal zone B cells and follicular dendritic cells to provide an optimal enhancement of antibody responses.
Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2015. , 52 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1061
IgE, IgM, IgG3, antibody responses, T-cell responses, antigen transportation, antigen presentation, complement, complement receptors 1 and 2
Immunology in the medical area
Research subject Immunology
IdentifiersURN: urn:nbn:se:uu:diva-237337ISBN: 978-91-554-9129-1OAI: oai:DiVA.org:uu-237337DiVA: diva2:769860
2015-02-12, C8:301, BMC, Husargatan 3, Uppsala, 09:15 (English)
Severinson, Eva, Professor
Heyman, Birgitta, Professor
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