A viral glycoprotein targets IgG+ memory B cells to mediate humoral immune evasion

Virus infections elicit long-term IgG antibody and memory responses. Human cytomegalovirus (HCMV) is widespread in humans and disseminates despite the presence of virus-specific antibodies. Here, we report that the HCMV Fcγ-binding glycoprotein 34 modulates humoral immunity by binding to IgG⁺ memory B cells. gp34-B cell receptor (BCR) interaction initiates activation of the PDK1/AKT/mTOR/S6 pathway and BCR internalization in a SYK-independent manner. Prolonged stimulation also induces B-cell activation via upregulation of CD69 and CD86. In a T-cell-dependent response, however, interaction with gp34 blocks B-cell proliferation, differentiation into plasmablasts, and soluble IgG production, while stimulating TNF-α secretion. Through gp34 stimulation on IgG⁺ B cells, neighboring IgM⁺ and IgA⁺ B cells are likewise impaired in proliferation, plasmablast formation, and immunoglobulin secretion. In summary, gp34 specifically interacts with IgG⁺ memory B cells, inducing a hyporesponsive state across the B-cell compartment through direct and indirect regulation. This reveals a novel mode of viral evasion from B-cell responses by suppressing secondary immunity.

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Publication Details

Journal
EMBO Molecular Medicine
Published
2026-01-20
DOI
https://doi.org/10.1038/s44321-026-00372-1
Citations
1
Primary Topic
Cytomegalovirus and herpesvirus research
Type
article
Field-Weighted Citation Impact
31.52

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article

A viral glycoprotein targets IgG+ memory B cells to mediate humoral immune evasion

Raquel Lorenzetti, Jens von Einem, Petra Hadlová, Marta Rizzi et al.
1 citations
EMBO Molecular Medicine
Cytomegalovirus and herpesvirus research
31.52
article

A viral glycoprotein targets IgG+ memory B cells to mediate humoral immune evasion

Raquel Lorenzetti, Jens von Einem, Petra Hadlová, Marta Rizzi, Julian Staniek, Iga Janowska, Katja Hoffmann, Bodo Plachter, Manuela Fiedler, Henrike Reinhard, Hartmut Hengel, Clarissa Read, Ann-Katrin Kohl, Tihana Lenac Rovis, Philipp Kolb, Valeria Falcone, Stefan F H Neys, Stipan Jonjic, Magdalena Huber
article en
1 citations

Abstract

Virus infections elicit long-term IgG antibody and memory responses. Human cytomegalovirus (HCMV) is widespread in humans and disseminates despite the presence of virus-specific antibodies. Here, we report that the HCMV Fcγ-binding glycoprotein 34 modulates humoral immunity by binding to IgG⁺ memory B cells. gp34-B cell receptor (BCR) interaction initiates activation of the PDK1/AKT/mTOR/S6 pathway and BCR internalization in a SYK-independent manner. Prolonged stimulation also induces B-cell activation via upregulation of CD69 and CD86. In a T-cell-dependent response, however, interaction with gp34 blocks B-cell proliferation, differentiation into plasmablasts, and soluble IgG production, while stimulating TNF-α secretion. Through gp34 stimulation on IgG⁺ B cells, neighboring IgM⁺ and IgA⁺ B cells are likewise impaired in proliferation, plasmablast formation, and immunoglobulin secretion. In summary, gp34 specifically interacts with IgG⁺ memory B cells, inducing a hyporesponsive state across the B-cell compartment through direct and indirect regulation. This reveals a novel mode of viral evasion from B-cell responses by suppressing secondary immunity.

EMBO Molecular MedicineVol. 18(2)
Beth Israel Deaconess Medical Center (US), University of Rijeka (HR), University of Freiburg (DE), Universität Ulm (DE), Johannes Gutenberg University Mainz (DE), Charles University (CZ), University Medical Center Freiburg (DE), Düsseldorf University Hospital (DE), University Medical Center of the Johannes Gutenberg University Mainz (DE), Institute of Immunology (HR), Berlin Institute of Health at Charité - Universitätsmedizin Berlin (DE), Heinrich Heine University Düsseldorf (DE), Medical University of Vienna (AT)
Deutsche Forschungsgemeinschaft, Hrvatska Zaklada za Znanost, European Regional Development Fund
Openalex Percentile: Top 2%
Cytomegalovirus and herpesvirus research
31.52
DOIOpen Access PDFOpenAlex
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