TY  - JOUR
AU  - Felixberger, Peter Tobias
AU  - Andrieux, Geoffroy
AU  - Maul-Pavicic, Andrea
AU  - Goldacker, Sigune
AU  - Harder, Ina
AU  - Gutenberger, Sylvia
AU  - Landry, Jonathan J M
AU  - Benes, Vladimir
AU  - Jakob, Till Fabian
AU  - Boerries, Melanie
AU  - Nitschke, Lars
AU  - Voll, Reinhard Edmund
AU  - Warnatz, Klaus
AU  - Keller, Baerbel
TI  - CD21low B cells reveal a unique glycosylation pattern with hypersialylation and hyperfucosylation.
JO  - Frontiers in immunology
VL  - 16
SN  - 1664-3224
CY  - Lausanne
PB  - Frontiers Media
M1  - DKFZ-2025-00450
SP  - 1512279
PY  - 2025
AB  - 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.
KW  - Humans
KW  - Glycosylation
KW  - Common Variable Immunodeficiency: immunology
KW  - Common Variable Immunodeficiency: metabolism
KW  - Male
KW  - Female
KW  - B-Lymphocytes: immunology
KW  - B-Lymphocytes: metabolism
KW  - Adult
KW  - Middle Aged
KW  - Fucose: metabolism
KW  - Protein Processing, Post-Translational
KW  - Interferon-gamma: metabolism
KW  - Sialic Acids: metabolism
KW  - Lymphocyte Activation: immunology
KW  - CD21low B cells (Other)
KW  - CVID (Other)
KW  - T-bet (Other)
KW  - anti-IgM/IFNγ (Other)
KW  - glycome (Other)
KW  - glycosylation (Other)
KW  - hyperfucosylation (Other)
KW  - hypersialylation (Other)
KW  - Fucose (NLM Chemicals)
KW  - Interferon-gamma (NLM Chemicals)
KW  - Sialic Acids (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:40013136
C2  - pmc:PMC11861550
DO  - DOI:10.3389/fimmu.2025.1512279
UR  - https://inrepo02.dkfz.de/record/299490
ER  -