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@ARTICLE{Felixberger:299490,
      author       = {P. T. Felixberger and G. Andrieux and A. Maul-Pavicic and
                      S. Goldacker and I. Harder and S. Gutenberger and J. J. M.
                      Landry and V. Benes and T. F. Jakob and M. Boerries$^*$ and
                      L. Nitschke and R. E. Voll and K. Warnatz and B. Keller},
      title        = {{CD}21low {B} cells reveal a unique glycosylation pattern
                      with hypersialylation and hyperfucosylation.},
      journal      = {Frontiers in immunology},
      volume       = {16},
      issn         = {1664-3224},
      address      = {Lausanne},
      publisher    = {Frontiers Media},
      reportid     = {DKFZ-2025-00450},
      pages        = {1512279},
      year         = {2025},
      abstract     = {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.},
      keywords     = {Humans / Glycosylation / Common Variable Immunodeficiency:
                      immunology / Common Variable Immunodeficiency: metabolism /
                      Male / Female / B-Lymphocytes: immunology / B-Lymphocytes:
                      metabolism / Adult / Middle Aged / Fucose: metabolism /
                      Protein Processing, Post-Translational / Interferon-gamma:
                      metabolism / Sialic Acids: metabolism / Lymphocyte
                      Activation: immunology / CD21low B cells (Other) / CVID
                      (Other) / T-bet (Other) / anti-IgM/IFNγ (Other) / glycome
                      (Other) / glycosylation (Other) / hyperfucosylation (Other)
                      / hypersialylation (Other) / Fucose (NLM Chemicals) /
                      Interferon-gamma (NLM Chemicals) / Sialic Acids (NLM
                      Chemicals)},
      cin          = {FR01},
      ddc          = {610},
      cid          = {I:(DE-He78)FR01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40013136},
      pmc          = {pmc:PMC11861550},
      doi          = {10.3389/fimmu.2025.1512279},
      url          = {https://inrepo02.dkfz.de/record/299490},
}