IgG Subclass Determines Suppression Versus Enhancement of Humoral Alloimmunity to Kell RBC Antigens in Mice
It has long been appreciated that immunoglobulins are not just the effector endpoint of humoral immunity, but rather have a complex role in regulating antibody responses themselves. Donor derived anti-RhD IgG has been used for over 50 years as an immunoprophylactic to prevent maternal alloimmunizati...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2020-07-01
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| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2020.01516/full |
| _version_ | 1818260530799837184 |
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| author | Paurvi Shinde Heather L. Howie Tamara C. Stegmann Ariel M. Hay Hayley R. Waterman Zoltan Szittner Arthur E. H. Bentlage Linda Kapp Suzanne N. Lissenberg-Thunnissen Gillian Dekkers Richard B. M. Schasfoort Sarah J. Ratcliffe Mark E. Smolkin Gestur Vidarsson C. Ellen van der Schoot Krystalyn E. Hudson James C. Zimring James C. Zimring |
| author_facet | Paurvi Shinde Heather L. Howie Tamara C. Stegmann Ariel M. Hay Hayley R. Waterman Zoltan Szittner Arthur E. H. Bentlage Linda Kapp Suzanne N. Lissenberg-Thunnissen Gillian Dekkers Richard B. M. Schasfoort Sarah J. Ratcliffe Mark E. Smolkin Gestur Vidarsson C. Ellen van der Schoot Krystalyn E. Hudson James C. Zimring James C. Zimring |
| author_sort | Paurvi Shinde |
| collection | DOAJ |
| description | It has long been appreciated that immunoglobulins are not just the effector endpoint of humoral immunity, but rather have a complex role in regulating antibody responses themselves. Donor derived anti-RhD IgG has been used for over 50 years as an immunoprophylactic to prevent maternal alloimmunization to RhD. Although anti-RhD has dramatically decreased rates of hemolytic disease of the fetus and newborn (for the RhD alloantigen), anti-RhD also fails in some cases, and can even paradoxically enhance immune responses in some circumstances. Attempts to generate a monoclonal anti-RhD have largely failed, with some monoclonals suppressing less than donor derived anti-RhD and others enhancing immunity. These difficulties likely result, in part, because the mechanism of anti-RhD remains unclear. However, substantial evidence exists to reject the common explanations of simple clearance of RhD + RBCs or masking of antigen. Donor derived anti-RhD is a mixture of 4 different IgG subtypes. To the best of our knowledge an analysis of the role different IgG subtypes play in immunoregulation has not been carried out; and, only IgG1 and IgG3 have been tested as monoclonals. Multiple attempts to elicit alloimmune responses to human RhD epitopes in mice have failed. To circumvent this limitation, we utilize a tractable animal model of RBC alloimmunization using the human Kell glycoprotein as an antigen to test the effect of IgG subtype on immunoregulation by antibodies to RBC alloantigens. We report that the ability of an anti-RBC IgG to enhance, suppress (at the level of IgM responses), or have no effect is a function of the IgG subclass in this model system. |
| first_indexed | 2024-12-12T18:32:48Z |
| format | Article |
| id | doaj.art-5ced9a8f9c86426f90e7e02309b97636 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-12T18:32:48Z |
| publishDate | 2020-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-5ced9a8f9c86426f90e7e02309b976362022-12-22T00:15:52ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-07-011110.3389/fimmu.2020.01516555984IgG Subclass Determines Suppression Versus Enhancement of Humoral Alloimmunity to Kell RBC Antigens in MicePaurvi Shinde0Heather L. Howie1Tamara C. Stegmann2Ariel M. Hay3Hayley R. Waterman4Zoltan Szittner5Arthur E. H. Bentlage6Linda Kapp7Suzanne N. Lissenberg-Thunnissen8Gillian Dekkers9Richard B. M. Schasfoort10Sarah J. Ratcliffe11Mark E. Smolkin12Gestur Vidarsson13C. Ellen van der Schoot14Krystalyn E. Hudson15James C. Zimring16James C. Zimring17Bloodworks Northwest Research Institute, Seattle, WA, United StatesDepartment of Pathology, Carter Immunology Center, University of Virginia School of Medicine, Charlottesville, VA, United StatesSanquin Research and Landsteiner Laboratory, Department of Experimental Immunohematology, Academic Medical Center, University of Amsterdam, Amsterdam, NetherlandsDepartment of Pathology, Carter Immunology Center, University of Virginia School of Medicine, Charlottesville, VA, United StatesBloodworks Northwest Research Institute, Seattle, WA, United StatesSanquin Research and Landsteiner Laboratory, Department of Experimental Immunohematology, Academic Medical Center, University of Amsterdam, Amsterdam, NetherlandsSanquin Research and Landsteiner Laboratory, Department of Experimental Immunohematology, Academic Medical Center, University of Amsterdam, Amsterdam, NetherlandsBloodworks Northwest Research Institute, Seattle, WA, United StatesSanquin Research and Landsteiner Laboratory, Department of Experimental Immunohematology, Academic Medical Center, University of Amsterdam, Amsterdam, NetherlandsSanquin Research and Landsteiner Laboratory, Department of Experimental Immunohematology, Academic Medical Center, University of Amsterdam, Amsterdam, NetherlandsMedical Cell Biophysics Group, MIRA Institute, University of Twente, Enschede, NetherlandsDepartment of Pathology, Carter Immunology Center, University of Virginia School of Medicine, Charlottesville, VA, United StatesDepartment of Pathology, Carter Immunology Center, University of Virginia School of Medicine, Charlottesville, VA, United StatesSanquin Research and Landsteiner Laboratory, Department of Experimental Immunohematology, Academic Medical Center, University of Amsterdam, Amsterdam, NetherlandsSanquin Research and Landsteiner Laboratory, Department of Experimental Immunohematology, Academic Medical Center, University of Amsterdam, Amsterdam, NetherlandsDepartment of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, NY, United StatesBloodworks Northwest Research Institute, Seattle, WA, United StatesDepartment of Pathology, Carter Immunology Center, University of Virginia School of Medicine, Charlottesville, VA, United StatesIt has long been appreciated that immunoglobulins are not just the effector endpoint of humoral immunity, but rather have a complex role in regulating antibody responses themselves. Donor derived anti-RhD IgG has been used for over 50 years as an immunoprophylactic to prevent maternal alloimmunization to RhD. Although anti-RhD has dramatically decreased rates of hemolytic disease of the fetus and newborn (for the RhD alloantigen), anti-RhD also fails in some cases, and can even paradoxically enhance immune responses in some circumstances. Attempts to generate a monoclonal anti-RhD have largely failed, with some monoclonals suppressing less than donor derived anti-RhD and others enhancing immunity. These difficulties likely result, in part, because the mechanism of anti-RhD remains unclear. However, substantial evidence exists to reject the common explanations of simple clearance of RhD + RBCs or masking of antigen. Donor derived anti-RhD is a mixture of 4 different IgG subtypes. To the best of our knowledge an analysis of the role different IgG subtypes play in immunoregulation has not been carried out; and, only IgG1 and IgG3 have been tested as monoclonals. Multiple attempts to elicit alloimmune responses to human RhD epitopes in mice have failed. To circumvent this limitation, we utilize a tractable animal model of RBC alloimmunization using the human Kell glycoprotein as an antigen to test the effect of IgG subtype on immunoregulation by antibodies to RBC alloantigens. We report that the ability of an anti-RBC IgG to enhance, suppress (at the level of IgM responses), or have no effect is a function of the IgG subclass in this model system.https://www.frontiersin.org/article/10.3389/fimmu.2020.01516/fullantibodyimmune regulationIgG subclassred blood cellalloimmunity |
| spellingShingle | Paurvi Shinde Heather L. Howie Tamara C. Stegmann Ariel M. Hay Hayley R. Waterman Zoltan Szittner Arthur E. H. Bentlage Linda Kapp Suzanne N. Lissenberg-Thunnissen Gillian Dekkers Richard B. M. Schasfoort Sarah J. Ratcliffe Mark E. Smolkin Gestur Vidarsson C. Ellen van der Schoot Krystalyn E. Hudson James C. Zimring James C. Zimring IgG Subclass Determines Suppression Versus Enhancement of Humoral Alloimmunity to Kell RBC Antigens in Mice Frontiers in Immunology antibody immune regulation IgG subclass red blood cell alloimmunity |
| title | IgG Subclass Determines Suppression Versus Enhancement of Humoral Alloimmunity to Kell RBC Antigens in Mice |
| title_full | IgG Subclass Determines Suppression Versus Enhancement of Humoral Alloimmunity to Kell RBC Antigens in Mice |
| title_fullStr | IgG Subclass Determines Suppression Versus Enhancement of Humoral Alloimmunity to Kell RBC Antigens in Mice |
| title_full_unstemmed | IgG Subclass Determines Suppression Versus Enhancement of Humoral Alloimmunity to Kell RBC Antigens in Mice |
| title_short | IgG Subclass Determines Suppression Versus Enhancement of Humoral Alloimmunity to Kell RBC Antigens in Mice |
| title_sort | igg subclass determines suppression versus enhancement of humoral alloimmunity to kell rbc antigens in mice |
| topic | antibody immune regulation IgG subclass red blood cell alloimmunity |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2020.01516/full |
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