CD21low B cells reveal a unique glycosylation pattern with hypersialylation and hyperfucosylation
BackgroundThe posttranslational modification of cellular macromolecules by glycosylation is considered to contribute to disease pathogenesis in autoimmune and inflammatory conditions. In a subgroup of patients with common variable immunodeficiency (CVID), the occurrence of such complications is asso...
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Frontiers Media S.A.
2025-02-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1512279/full |
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| author | Peter Tobias Felixberger Peter Tobias Felixberger Geoffroy Andrieux Andrea Maul-Pavicic Andrea Maul-Pavicic Sigune Goldacker Sigune Goldacker Ina Harder Ina Harder Sylvia Gutenberger Sylvia Gutenberger Jonathan J. M. Landry Vladimir Benes Till Fabian Jakob Melanie Boerries Melanie Boerries Lars Nitschke Reinhard Edmund Voll Reinhard Edmund Voll Klaus Warnatz Klaus Warnatz Baerbel Keller Baerbel Keller |
| author_facet | Peter Tobias Felixberger Peter Tobias Felixberger Geoffroy Andrieux Andrea Maul-Pavicic Andrea Maul-Pavicic Sigune Goldacker Sigune Goldacker Ina Harder Ina Harder Sylvia Gutenberger Sylvia Gutenberger Jonathan J. M. Landry Vladimir Benes Till Fabian Jakob Melanie Boerries Melanie Boerries Lars Nitschke Reinhard Edmund Voll Reinhard Edmund Voll Klaus Warnatz Klaus Warnatz Baerbel Keller Baerbel Keller |
| author_sort | Peter Tobias Felixberger |
| collection | DOAJ |
| description | BackgroundThe posttranslational modification of cellular macromolecules by glycosylation is considered to contribute to disease pathogenesis in autoimmune and inflammatory conditions. In a subgroup of patients with common variable immunodeficiency (CVID), the occurrence of such complications is associated with an expansion of naïve-like CD21low B cells during a chronic type 1 immune activation. The glycosylation pattern of B cells in CVID patients has not been addressed to date.ObjectiveThe objective of this study was to examine the surface glycome of B cells in patients with CVID and associated immune dysregulation.MethodsWe performed surface lectin staining on B cells from peripheral blood and tonsils, both ex vivo and after in vitro stimulation. Additionally, we examined the expression of glycosylation-related genes by RNAseq in naïve-like CD21low B cells ex vivo, as well as in naïve CD21pos B cells from healthy controls after in vitro stimulation.ResultsUnlike CD21pos B cells, naïve-like CD21low B cells from CVID patients and CD21low B cells from healthy controls exhibited a unique glycosylation pattern with high levels of α2,6 sialic acids and fucose. This hypersialylation and hyperfucosylation were particularly induced by activation with anti-IgM and interferon-γ (IFN-γ). Transcriptome analysis suggested that naïve-like CD21low B cells possess a comprehensively reorganised glycosylation machinery, with anti-IgM/IFN-γ having the potential to initiate these changes in vitro.ConclusionCD21low B cells are hypersialylated and hyperfucosylated. This may implicate altered lectin-ligand interactions on the cell surface potentially affecting the CD21low B-cell function. These glycome changes appear to be driven by the prominent type I immune response in complicated CVID patients. A better understanding of how altered glycosylation influences immune cell function could lead to new therapeutic strategies. |
| format | Article |
| id | doaj-art-4376dd6e6c6a4f1b9793bdd3d9dd8514 |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj-art-4376dd6e6c6a4f1b9793bdd3d9dd85142025-02-12T07:26:42ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-02-011610.3389/fimmu.2025.15122791512279CD21low B cells reveal a unique glycosylation pattern with hypersialylation and hyperfucosylationPeter Tobias Felixberger0Peter Tobias Felixberger1Geoffroy Andrieux2Andrea Maul-Pavicic3Andrea Maul-Pavicic4Sigune Goldacker5Sigune Goldacker6Ina Harder7Ina Harder8Sylvia Gutenberger9Sylvia Gutenberger10Jonathan J. M. Landry11Vladimir Benes12Till Fabian Jakob13Melanie Boerries14Melanie Boerries15Lars Nitschke16Reinhard Edmund Voll17Reinhard Edmund Voll18Klaus Warnatz19Klaus Warnatz20Baerbel Keller21Baerbel Keller22Department of Rheumatology and Clinical Immunology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, GermanyCenter for Chronic Immunodeficiency (CCI), Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, GermanyInstitute of Medical Bioinformatics and Systems Medicine, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, GermanyDepartment of Rheumatology and Clinical Immunology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, GermanyCenter for Chronic Immunodeficiency (CCI), Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, GermanyDepartment of Rheumatology and Clinical Immunology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, GermanyCenter for Chronic Immunodeficiency (CCI), Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, GermanyDepartment of Rheumatology and Clinical Immunology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, GermanyCenter for Chronic Immunodeficiency (CCI), Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, GermanyDepartment of Rheumatology and Clinical Immunology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, GermanyCenter for Chronic Immunodeficiency (CCI), Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, GermanyGenomics Core Facility, European Molecular Biology Laboratory, Heidelberg, GermanyGenomics Core Facility, European Molecular Biology Laboratory, Heidelberg, GermanyDepartment of Oto-Rhino-Laryngology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, GermanyInstitute of Medical Bioinformatics and Systems Medicine, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, GermanyGerman Cancer Consortium (DKTK), Partner site Freiburg, a partnership between DKFZ and Medical Center - University of Freiburg, Freiburg, GermanyDivision of Genetics, Department of Biology, University of Erlangen, Erlangen, GermanyDepartment of Rheumatology and Clinical Immunology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, GermanyCenter for Chronic Immunodeficiency (CCI), Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, GermanyDepartment of Rheumatology and Clinical Immunology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, GermanyCenter for Chronic Immunodeficiency (CCI), Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, GermanyDepartment of Rheumatology and Clinical Immunology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, GermanyCenter for Chronic Immunodeficiency (CCI), Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, GermanyBackgroundThe posttranslational modification of cellular macromolecules by glycosylation is considered to contribute to disease pathogenesis in autoimmune and inflammatory conditions. In a subgroup of patients with common variable immunodeficiency (CVID), the occurrence of such complications is associated with an expansion of naïve-like CD21low B cells during a chronic type 1 immune activation. The glycosylation pattern of B cells in CVID patients has not been addressed to date.ObjectiveThe objective of this study was to examine the surface glycome of B cells in patients with CVID and associated immune dysregulation.MethodsWe performed surface lectin staining on B cells from peripheral blood and tonsils, both ex vivo and after in vitro stimulation. Additionally, we examined the expression of glycosylation-related genes by RNAseq in naïve-like CD21low B cells ex vivo, as well as in naïve CD21pos B cells from healthy controls after in vitro stimulation.ResultsUnlike CD21pos B cells, naïve-like CD21low B cells from CVID patients and CD21low B cells from healthy controls exhibited a unique glycosylation pattern with high levels of α2,6 sialic acids and fucose. This hypersialylation and hyperfucosylation were particularly induced by activation with anti-IgM and interferon-γ (IFN-γ). Transcriptome analysis suggested that naïve-like CD21low B cells possess a comprehensively reorganised glycosylation machinery, with anti-IgM/IFN-γ having the potential to initiate these changes in vitro.ConclusionCD21low B cells are hypersialylated and hyperfucosylated. This may implicate altered lectin-ligand interactions on the cell surface potentially affecting the CD21low B-cell function. These glycome changes appear to be driven by the prominent type I immune response in complicated CVID patients. A better understanding of how altered glycosylation influences immune cell function could lead to new therapeutic strategies.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1512279/fullCD21low B cellsCVIDglycomeglycosylationhypersialylationhyperfucosylation |
| spellingShingle | Peter Tobias Felixberger Peter Tobias Felixberger Geoffroy Andrieux Andrea Maul-Pavicic Andrea Maul-Pavicic Sigune Goldacker Sigune Goldacker Ina Harder Ina Harder Sylvia Gutenberger Sylvia Gutenberger Jonathan J. M. Landry Vladimir Benes Till Fabian Jakob Melanie Boerries Melanie Boerries Lars Nitschke Reinhard Edmund Voll Reinhard Edmund Voll Klaus Warnatz Klaus Warnatz Baerbel Keller Baerbel Keller CD21low B cells reveal a unique glycosylation pattern with hypersialylation and hyperfucosylation Frontiers in Immunology CD21low B cells CVID glycome glycosylation hypersialylation hyperfucosylation |
| title | CD21low B cells reveal a unique glycosylation pattern with hypersialylation and hyperfucosylation |
| title_full | CD21low B cells reveal a unique glycosylation pattern with hypersialylation and hyperfucosylation |
| title_fullStr | CD21low B cells reveal a unique glycosylation pattern with hypersialylation and hyperfucosylation |
| title_full_unstemmed | CD21low B cells reveal a unique glycosylation pattern with hypersialylation and hyperfucosylation |
| title_short | CD21low B cells reveal a unique glycosylation pattern with hypersialylation and hyperfucosylation |
| title_sort | cd21low b cells reveal a unique glycosylation pattern with hypersialylation and hyperfucosylation |
| topic | CD21low B cells CVID glycome glycosylation hypersialylation hyperfucosylation |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1512279/full |
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