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<p>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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月20日

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  • 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

摘要

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.