CD21low B cells reveal a unique glycosylation pattern with hypersialylation and hyperfucosylation

Felixberger PT, Andrieux G, Maul-Pavicic A, Goldacker S, Harder I, Gutenberger S, Landry JJ, Benes V, Jakob TF, Boerries M, Nitschke L, Voll RE, Warnatz K, Keller B (2025)

Publication Type: Journal article

Publication year: 2025

Journal

Frontiers in Immunology Frontiers Research Foundation / Frontiers Media

Book Volume: 16

Article Number: 1512279

DOI: 10.3389/fimmu.2025.1512279

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 CD21^low 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 CD21^low B cells ex vivo, as well as in naïve CD21^pos B cells from healthy controls after in vitro stimulation. Results: Unlike CD21^pos B cells, naïve-like CD21^low B cells from CVID patients and CD21^low 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 CD21^low B cells possess a comprehensively reorganised glycosylation machinery, with anti-IgM/IFN-γ having the potential to initiate these changes in vitro. Conclusion: CD21^low B cells are hypersialylated and hyperfucosylated. This may implicate altered lectin-ligand interactions on the cell surface potentially affecting the CD21^low 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.

Authors with CRIS profile

Lars Nitschke Professur für Genetik

Involved external institutions

Universitätsklinikum Freiburg

Germany (DE) European Molecular Biology Laboratory (EMBL)

Germany (DE)

How to cite

APA:

Felixberger, P.T., Andrieux, G., Maul-Pavicic, A., Goldacker, S., Harder, I., Gutenberger, S.,... Keller, B. (2025). CD21low B cells reveal a unique glycosylation pattern with hypersialylation and hyperfucosylation. Frontiers in Immunology, 16. https://doi.org/10.3389/fimmu.2025.1512279

MLA:

Felixberger, Peter Tobias, et al. "CD21low B cells reveal a unique glycosylation pattern with hypersialylation and hyperfucosylation." Frontiers in Immunology 16 (2025).

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