Bibliographic Details
Title: |
CD21low B cells reveal a unique glycosylation pattern with hypersialylation and hyperfucosylation. |
Authors: |
Felixberger, Peter Tobias, Andrieux, Geoffroy, Maul-Pavicic, Andrea, Goldacker, Sigune, Harder, Ina, Gutenberger, Sylvia, Landry, Jonathan J. M., Benes, Vladimir, Jakob, Till Fabian, Boerries, Melanie, Nitschke, Lars, Voll, Reinhard Edmund, Warnatz, Klaus, Keller, Baerbel |
Source: |
Frontiers in Immunology; 2025, p1-14, 14p |
Subject Terms: |
B cells, COMMON variable immunodeficiency, CELL physiology, SIALIC acids, IMMUNE response |
Abstract: |
Background: The 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. Objective: The objective of this study was to examine the surface glycome of B cells in patients with CVID and associated immune dysregulation. Methods: We 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. Results: Unlike 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. Conclusion: CD21low 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. [ABSTRACT FROM AUTHOR] |
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Database: |
Complementary Index |