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

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⁺

SUBMITTER: Cramer P 

PROVIDER: S-EPMC12905349 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature