#3-41E. The Viral Driver: How EBV Reprograms Autoreactive B Cells in Lupus (Sci Transl Med, 2025)

While the epidemiological association between Epstein-Barr virus (EBV) and Systemic Lupus Erythematosus (SLE) is well-recognized, the precise mechanism by which this ubiquitous virus drives systemic autoimmunity has remained elusive. This study utilizes a novel single-cell sequencing platform, EBV-seq, to demonstrate that EBV selectively infects autoreactive B cells and reprograms them via EBNA2 into potent antigen-presenting cells. The most significant finding is that these rare EBV-positive cells act as pathogenic "drivers" that activate T peripheral helper cells, which subsequently orchestrate the expansion and affinity maturation of uninfected autoreactive B cell clones. This provides a mechanistic basis for how a latent viral infection can propagate broad autoimmune responses. However, when interpreting these results, it is important to note the study's reliance on frozen PBMCs, which may limit the sensitivity of viral gene detection and the characterization of specific latency phases compared to fresh samples. For physicians, these findings reinforce the theoretical framework supporting deep B cell depletion strategies, such as CD19-CAR T cell therapy, and suggest that future interventions targeting the EBV-infected B cell reservoir specifically could offer a pathway to durable remission in SLE.

Citation: YOUNIS, S. et al. Epstein-Barr virus reprograms autoreactive B cells as antigen-presenting cells in systemic lupus erythematosus. Science Translational Medicine. 2025. DOI: 10.1126/scitranslmed.ady0210

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