Anti-FcγRIIB (CD32) Antibodies Differentially Modulate Murine FVIII-Specific Recall Responsein vitro
| Autor: | Sonja Werwitzke, Julia Friese, S. Bergmann, Andreas Tiede, Nadine Vollack, Mark S. Cragg |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
congenital hereditary and neonatal diseases and abnormalities CD32 Time Factors medicine.drug_class animal diseases medicine.medical_treatment T cell Immunology Bone Marrow Cells Biology Monoclonal antibody Interferon-gamma 03 medical and health sciences Immune system hemic and lymphatic diseases medicine Animals Lymphocytes Receptor Memory B cell Cells Cultured Mice Knockout B-Lymphocytes Factor VIII Receptors IgG Antibodies Monoclonal Dendritic Cells General Medicine Flow Cytometry Molecular biology Interleukin-10 Mice Inbred C57BL 030104 developmental biology Cytokine medicine.anatomical_structure Immunoglobulin G biology.protein Antibody Immunologic Memory Spleen |
| Zdroj: | Scandinavian Journal of Immunology. 86:91-99 |
| ISSN: | 0300-9475 |
| DOI: | 10.1111/sji.12573 |
| Popis: | Fc gamma receptors (FcγRs) for IgG regulate adaptive immune responses by modulating activating and inhibitory signaling pathways within immune cells. Data from a hemophilia A mouse model demonstrate that genetic deletion or blockade of the inhibitory FcγR (CD32) suppresses the formation of antibody secreting cells (ASCs) in vitro. Mechanisms preventing the FVIII-specific recall response, however, remain unclear. Here, the potential role of CD32 inhibition was studied by differentially modulating receptor activity with selected anti-CD32 monoclonal antibodies (mAbs). Splenocytes from immunized FVIII-/- mice were re-stimulated with FVIII in the absence or presence of different anti-CD32 mAbs over 6 days. At day 6, cytokine release was quantified from cell culture supernatant and the formation of FVIII-specific ASCs assessed. Binding of FVIII-containing immune complexes (F8-ICs) to bone marrow derived dendritic cells (BMdDCs) was also investigated. The antagonistic CD32 mAb AT128 suppressed the formation of FVIII-specific ASCs and reduced secretion of IFN-γ and IL-10. In contrast, the agonistic mAbs AT130-2 and AT130-5, and their F(ab’)2 fragments, allowed the formation of FVIII-specific ASCs, even though the full IgG of AT130-2 reduced binding of F8-ICs to CD32. Data suggest that an inhibitory signal is transmitted when F8-ICs bind to CD32 and that this signal is required during memory B cell (MBC) activation to support formation of FVIII-specific ASCs. If the inhibitory signal is lacking due to CD32 deletion or blockade with antagonistic anti-CD32 mAbs, FVIII-specific T cell stimulation and ASC formation are suppressed, whereas agonistic stimulation of CD32 restores T cell stimulation and ASC formation. This article is protected by copyright. All rights reserved. |
| Databáze: | OpenAIRE |
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