Year: 2026
Type: article
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.
Source: EMBO Molecular Medicine
Authors: Precious Cramer, Stefan F H Neys, Manuela Fiedler, Raquel Lorenzetti, Henrike Reinhard, Iga Janowska, Julian Staniek, Ann-Katrin Kohl, Petra Hadlova, Magdalena Huber, Bodo Plachter, Clarissa Read, Valeria Falcone, Jens von Einem, Katja Hoffmann, Tihana Lenac Rovis, Stipan Jonjic, Philipp Kolb, Marta Rizzi, Hartmut Hengel
Institutions: Beth Israel Deaconess Medical Center, University of Freiburg, University Medical Center Freiburg, Düsseldorf University Hospital, Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Heinrich Heine University Düsseldorf, Charité - Universitätsmedizin Berlin, Charles University, Medical University of Vienna, Johannes Gutenberg University Mainz, University Medical Center of the Johannes Gutenberg University Mainz, Universität Ulm, University Hospital Ulm, University of Rijeka
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $7,990
Awards: G1078610655, G19327879, G2008309395, G2171898597, G2905322300, G293965311, G3890793441, G4628688569, G4925376223, Kontrolle der Schicksalsentscheidungen menschlicher BZellen, G641187091, G6462038999, G681575759, G7738337847, The immunoregulatory role of PrPC in antiviral immune response following cytomegaloviral infection
OpenAlex ID: W7124851713