Academic Journal
A viral glycoprotein targets IgG+ memory B cells to mediate humoral immune evasion
| Title: | A viral glycoprotein targets IgG+ memory B cells to mediate humoral immune evasion |
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| 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 |
| Source: | EMBO Mol Med |
| Publisher Information: | Springer Science and Business Media LLC, 2026. |
| Publication Year: | 2026 |
| Subject Terms: | Article |
| Description: | 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. |
| Document Type: | Article |
| Language: | English |
| ISSN: | 1757-4684 |
| DOI: | 10.1038/s44321-026-00372-1 |
| Access URL: | https://pubmed.ncbi.nlm.nih.gov/41559372 https://pubmed.ncbi.nlm.nih.gov/41559372/ https://doi.org/10.1038/s44321-026-00372-1 https://pmc.ncbi.nlm.nih.gov/articles/PMC12905349/ |
| Rights: | CC BY |
| Accession Number: | edsair.doi.dedup.....bf920dfeca8ce96c3b4234ed27a6eb87 |
| Database: | OpenAIRE |
| ISSN: | 17574684 |
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| DOI: | 10.1038/s44321-026-00372-1 |