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Ding, Zhoujie
Publications (10 of 18) Show all publications
Zhang, L., Ding, Z. & Heyman, B. (2017). IgG3-antigen complexes are deposited on follicular dendritic cells in the presence of C1q and C3. Scientific Reports, 7, Article ID 5400.
Open this publication in new window or tab >>IgG3-antigen complexes are deposited on follicular dendritic cells in the presence of C1q and C3
2017 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 5400Article in journal (Refereed) Published
Abstract [en]

IgG3, passively administered together with small proteins, induces enhanced primary humoral responses against these proteins. We previously found that, within 2 h of immunization, marginal zone (MZ) B cells capture IgG3-antigen complexes and transport them into splenic follicles and that this requires the presence of complement receptors 1 and 2. We have here investigated the localization of IgG3 anti-2, 4, 6-trinitrophenyl (TNP)/biotin-ovalbumin-TNP immune complexes in the follicles and the involvement of classical versus total complement activation in this process. The majority (50-90%) of antigen inside the follicles of mice immunized with IgG3-antigen complexes co-localized with the follicular dendritic cell (FDC) network. Capture of antigen by MZ B cells as well as antigen deposition on FDC was severely impaired in mice lacking C1q or C3, and lack of either C1q or C3 also impaired the ability of IgG3 to enhance antibody responses. Finally, IgG3 efficiently primed for a memory response against small proteins as well as against the large protein keyhole limpet hemocyanine.

National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:uu:diva-333611 (URN)10.1038/s41598-017-05704-3 (DOI)000405464200037 ()28710441 (PubMedID)
Funder
Swedish Research CouncilKing Gustaf V Jubilee Fund
Available from: 2017-11-16 Created: 2017-11-16 Last updated: 2017-11-16Bibliographically approved
Ding, Z., Dahlin, J. S., Xu, H. & Heyman, B. (2016). IgE-mediated enhancement of CD4(+) T cell responses requires antigen presentation by CD8 alpha(-) conventional dendritic cells. Scientific Reports, 6, Article ID 28290.
Open this publication in new window or tab >>IgE-mediated enhancement of CD4(+) T cell responses requires antigen presentation by CD8 alpha(-) conventional dendritic cells
2016 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, article id 28290Article in journal (Refereed) Published
Abstract [en]

IgE, forming an immune complex with small proteins, can enhance the specific antibody and CD4(+) T cell responses in vivo. The effects require the presence of CD23 (Fc epsilon-receptor II)(+) B cells, which capture IgE-complexed antigens (Ag) in the circulation and transport them to splenic B cell follicles. In addition, also CD11c(+) cells, which do not express CD23, are required for IgE-mediated enhancement of T cell responses. This suggests that some type of dendritic cell obtains IgE-Ag complexes from B cells and presents antigenic peptides to T cells. To elucidate the nature of this dendritic cell, mice were immunized with ovalbumin (OVA)-specific IgE and OVA, and different populations of CD11c(+) cells, obtained from the spleens four hours after immunization, were tested for their ability to present OVA. CD8 alpha(-) conventional dendritic cells (cDCs) were much more efficient in inducing specific CD4(+) T cell proliferation ex vivo than were CD8 alpha(+) cDCs or plasmacytoid dendritic cells. Thus, IgE-Ag complexes administered intravenously are rapidly transported to the spleen by recirculating B cells where they are delivered to CD8 alpha(-) cDCs which induce proliferation of CD4(+) T cells.

National Category
Immunology in the medical area
Identifiers
urn:nbn:se:uu:diva-299721 (URN)10.1038/srep28290 (DOI)000378108400001 ()27306570 (PubMedID)
Funder
Swedish Research Council
Available from: 2016-07-26 Created: 2016-07-26 Last updated: 2018-01-10Bibliographically approved
Thyagarajan, R., Banday, V., Ding, Z. & Lejon, K. (2015). Contribution of autoallergy to the pathogenesis in the NOD mice. Autoimmunity, 48(5), 298-304
Open this publication in new window or tab >>Contribution of autoallergy to the pathogenesis in the NOD mice
2015 (English)In: Autoimmunity, ISSN 0891-6934, E-ISSN 1607-842X, Vol. 48, no 5, p. 298-304Article in journal (Refereed) Published
Abstract [en]

The immunoglobulin isotype IgE is commonly associated with allergy. However, its involvement in autoimmune disease in general, and Type 1 diabetes (T1D) in particular, is still not completely clarified, nonetheless IgE has been observed in patients with T1D. In this article, we aimed to elucidate the contribution of IgE in the pathogenesis of the disease in a spontaneous model for T1D, i.e. the NOD mouse. We observed increased levels of IgE in splenic, lymph node and peripheral blood B cells in the NOD mice compared to the control C57BL/6 (B6) mice. No correlation was found between the IgE levels on B cells and those in the sera of these mice, indicating a B cell intrinsic property mediating IgE capture in NOD. Functionally, the B cells from NOD were similar to B6 in rescuing the IgE-mediated immune response via the low affinity receptor CD23 in a transgenic adoptive transfer system. However, the involvement of IgE in diabetes development was clearly demonstrated, as treatment with anti-IgE antibodies delayed the incidence of the diabetes in the NOD mice compared to the PBS treated group. Pancreas sections from a 13-week-old NOD revealed the presence of tertiary lymphoid structures with T cells, B cells, germinal centers and IgE suggesting the presence of autoantigen specific IgE. Our study provides an insight to the commonly overlooked immunoglobulin IgE and its potential role in autoimmunity.

Keywords
Autoallergy, B lymphocytes, IgE, NOD mouse, Type 1 diabetes
National Category
Immunology in the medical area
Identifiers
urn:nbn:se:uu:diva-261967 (URN)10.3109/08916934.2015.1016220 (DOI)000359797600004 ()25707684 (PubMedID)
Funder
Swedish Diabetes AssociationSwedish Child Diabetes FoundationLars Hierta Memorial Foundation
Available from: 2015-09-14 Created: 2015-09-07 Last updated: 2018-01-11Bibliographically approved
Dahlin, J. S., Ding, Z. & Hallgren, J. (2015). Distinguishing Mast Cell Progenitors from Mature Mast Cells in Mice. Stem Cells and Development, 24(14), 1703-1711
Open this publication in new window or tab >>Distinguishing Mast Cell Progenitors from Mature Mast Cells in Mice
2015 (English)In: Stem Cells and Development, ISSN 1547-3287, E-ISSN 1557-8534, Vol. 24, no 14, p. 1703-1711Article in journal (Refereed) Published
Abstract [en]

Mast cells originate from the bone marrow and develop into c-kit(+) FcRI(+) cells. Both mast cell progenitors (MCp) and mature mast cells express these cell surface markers, and ways validated to distinguish between the two maturation forms with flow cytometry have been lacking. Here, we show that primary peritoneal MCp from naive mice expressed high levels of integrin 7 and had a low side scatter (SSC) light profile; whereas mature mast cells expressed lower levels of integrin 7 and had a high SSC light profile. The maturation statuses of the cells were confirmed using three main strategies: (1) MCp, but not mature mast cells, were shown to be depleted by sublethal whole-body -irradiation. (2) The MCp were small and immature in terms of granule formation, whereas the mature mast cells were larger and had fully developed metachromatic granules. (3) The MCp had fewer transcripts of mast cell-specific proteases and the enzyme responsible for sulfation of heparin than mature mast cells. Moreover, isolated peritoneal MCp gave rise to mast cells when cultured in vitro. To summarize, we have defined MCp and mature mast cells in naive mice by flow cytometry. Using this strategy, mast cell maturation can be studied in vivo.

National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-265939 (URN)10.1089/scd.2014.0553 (DOI)000362083800007 ()25744159 (PubMedID)
Funder
The Royal Swedish Academy of SciencesSwedish Research Council
Available from: 2015-11-04 Created: 2015-11-04 Last updated: 2018-01-10Bibliographically approved
Ding, Z. (2015). Feedback Enhancement of Immune Responses by IgE, IgM, and IgG3 Antibodies. (Doctoral dissertation). Uppsala: Acta Universitatis Upsaliensis
Open this publication in new window or tab >>Feedback Enhancement of Immune Responses by IgE, IgM, and IgG3 Antibodies
2015 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

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. p. 52
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1061
Keywords
IgE, IgM, IgG3, antibody responses, T-cell responses, antigen transportation, antigen presentation, complement, complement receptors 1 and 2
National Category
Immunology in the medical area
Research subject
Immunology
Identifiers
urn:nbn:se:uu:diva-237337 (URN)978-91-554-9129-1 (ISBN)
Public defence
2015-02-12, C8:301, BMC, Husargatan 3, Uppsala, 09:15 (English)
Opponent
Supervisors
Available from: 2015-01-19 Created: 2014-12-01 Last updated: 2018-01-11Bibliographically approved
Bergman, A., Ding, Z. & Heyman, B. (2014). Antigen-Specific IgM Causes Deposition of C3 on Sheep Red Blood Cells Within Seconds After Immunization. Paper presented at 42nd Annual Meeting of the Scandinavian-Society-for-Immunology (SSI), JUN 11-14, 2014, Reykjavik, ICELAND. Scandinavian Journal of Immunology, 79(6), 442-442
Open this publication in new window or tab >>Antigen-Specific IgM Causes Deposition of C3 on Sheep Red Blood Cells Within Seconds After Immunization
2014 (English)In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 79, no 6, p. 442-442Article in journal, Meeting abstract (Other academic) Published
National Category
Microbiology in the medical area
Identifiers
urn:nbn:se:uu:diva-228893 (URN)000337588500053 ()
Conference
42nd Annual Meeting of the Scandinavian-Society-for-Immunology (SSI), JUN 11-14, 2014, Reykjavik, ICELAND
Available from: 2014-07-22 Created: 2014-07-22 Last updated: 2018-01-11Bibliographically approved
Henningsson, F., Ding, Z. & Heyman, B. (2014). B Cell-mediated Antigen Transport to Splenic Follicles [Letter to the editor]. Scandinavian Journal of Immunology, 79(1), 73-74
Open this publication in new window or tab >>B Cell-mediated Antigen Transport to Splenic Follicles
2014 (English)In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 79, no 1, p. 73-74Article in journal, Letter (Refereed) Published
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-216248 (URN)10.1111/sji.12125 (DOI)000328598900010 ()
Available from: 2014-01-20 Created: 2014-01-20 Last updated: 2017-12-06Bibliographically approved
Ding, Z., Bergman, A., Rutemark, C., Ouchida, R., Ohno, H., Wang, J.-Y. & Heyman, B. (2014). Divergent Regulation of B and T Cell Responses by Complement-Activating IgM. Paper presented at 42nd Annual Meeting of the Scandinavian-Society-for-Immunology (SSI), JUN 11-14, 2014, Reykjavik, ICELAND. Scandinavian Journal of Immunology, 79(6), 442-442
Open this publication in new window or tab >>Divergent Regulation of B and T Cell Responses by Complement-Activating IgM
Show others...
2014 (English)In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 79, no 6, p. 442-442Article in journal, Meeting abstract (Other academic) Published
National Category
Microbiology in the medical area
Identifiers
urn:nbn:se:uu:diva-228894 (URN)000337588500052 ()
Conference
42nd Annual Meeting of the Scandinavian-Society-for-Immunology (SSI), JUN 11-14, 2014, Reykjavik, ICELAND
Available from: 2014-07-22 Created: 2014-07-22 Last updated: 2018-01-11Bibliographically approved
Sörman, A., Zhang, L., Ding, Z. & Heyman, B. (2014). How antibodies use complement to regulate antibody responses. Molecular Immunology, 61(2), 79-88
Open this publication in new window or tab >>How antibodies use complement to regulate antibody responses
2014 (English)In: Molecular Immunology, ISSN 0161-5890, E-ISSN 1872-9142, Vol. 61, no 2, p. 79-88Article, review/survey (Refereed) Published
Abstract [en]

Antibodies, forming immune complexes with their specific antigen, can cause complete suppression or several 100-fold enhancement of the antibody response. Immune complexes containing IgG and IgM may activate complement and in such situations also complement components will be part of the immune complex. Here, we review experimental data on how antibodies via the complement system upregulate specific antibody responses. Current data suggest that murine IgG1, IgG2a, and IgG2b upregulate antibody responses primarily via Fc-receptors and not via complement. In contrast, IgM and IgG3 act via complement and require the presence of complement receptors 1 and 2 (CR1/2) expressed on both B cells and follicular dendritic cells. Complement plays a crucial role for antibody responses not only to antigen complexed to antibodies, but also to antigen administered alone. Lack of C1q, but not of Factor B or MBL, severely impairs antibody responses suggesting involvement of the classical pathway. In spite of this, normal antibody responses are found in mice lacking several activators of the classical pathway (complement activating natural IgM, serum amyloid P component (SAP), specific intracellular adhesion molecule-grabbing non-integrin R1 (SIGN-R1) or C-reactive protein. Possible explanations to these observations will be discussed.

Keywords
Complement receptor 1, Complement receptor 2, IgG3, mutant IgM
National Category
Immunology in the medical area Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:uu:diva-235585 (URN)10.1016/j.molimm.2014.06.010 (DOI)000342265300005 ()
Available from: 2014-11-06 Created: 2014-11-06 Last updated: 2018-01-11Bibliographically approved
Ding, Z., Zhang, L., Xu, H. & Heyman, B. (2014). IgG3-mediated enhancement of antibody responses is dependent on expression of complement receptors 1 and 2. Paper presented at 25th International Complement Workshop, SEP 14-18, 2014, Rio de Janeiro, BRAZIL. Molecular Immunology, 61(2), 277-278
Open this publication in new window or tab >>IgG3-mediated enhancement of antibody responses is dependent on expression of complement receptors 1 and 2
2014 (English)In: Molecular Immunology, ISSN 0161-5890, E-ISSN 1872-9142, Vol. 61, no 2, p. 277-278Article in journal, Meeting abstract (Other academic) Published
National Category
Immunology in the medical area Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:uu:diva-235590 (URN)000342265300193 ()
Conference
25th International Complement Workshop, SEP 14-18, 2014, Rio de Janeiro, BRAZIL
Available from: 2014-11-06 Created: 2014-11-06 Last updated: 2018-01-11Bibliographically approved
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