%0 Journal Article
%A Felixberger, Peter Tobias
%A Andrieux, Geoffroy
%A Maul-Pavicic, Andrea
%A Goldacker, Sigune
%A Harder, Ina
%A Gutenberger, Sylvia
%A Landry, Jonathan J M
%A Benes, Vladimir
%A Jakob, Till Fabian
%A Boerries, Melanie
%A Nitschke, Lars
%A Voll, Reinhard Edmund
%A Warnatz, Klaus
%A Keller, Baerbel
%T CD21low B cells reveal a unique glycosylation pattern with hypersialylation and hyperfucosylation.
%J Frontiers in immunology
%V 16
%@ 1664-3224
%C Lausanne
%I Frontiers Media
%M DKFZ-2025-00450
%P 1512279
%D 2025
%X 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.The objective of this study was to examine the surface glycome of B cells in patients with CVID and associated immune dysregulation.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.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.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.
%K Humans
%K Glycosylation
%K Common Variable Immunodeficiency: immunology
%K Common Variable Immunodeficiency: metabolism
%K Male
%K Female
%K B-Lymphocytes: immunology
%K B-Lymphocytes: metabolism
%K Adult
%K Middle Aged
%K Fucose: metabolism
%K Protein Processing, Post-Translational
%K Interferon-gamma: metabolism
%K Sialic Acids: metabolism
%K Lymphocyte Activation: immunology
%K CD21low B cells (Other)
%K CVID (Other)
%K T-bet (Other)
%K anti-IgM/IFNγ (Other)
%K glycome (Other)
%K glycosylation (Other)
%K hyperfucosylation (Other)
%K hypersialylation (Other)
%K Fucose (NLM Chemicals)
%K Interferon-gamma (NLM Chemicals)
%K Sialic Acids (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:40013136
%2 pmc:PMC11861550
%R 10.3389/fimmu.2025.1512279
%U https://inrepo02.dkfz.de/record/299490