How EBV Reprograms B Cells to Trigger Lupus

Most people in the world become infected with Epstein-Barr virus (EBV). Yet, this infection is often not symptomatic or can be mistaken for other childhood illnesses. Scientists have long linked this virus to autoimmune diseases, such as lupus, and long COVID, but the mechanisms behind this connection have remained unclear. What is clear though is that not everyone infected with EBV develops these illnesses, but just about everyone with lupus has been infected by EBV.

Now, a new study looks at what happens to B cells infected by EBV. Normally these B cells act as “antigen-presenting cells” where they process pieces of invading microbes, display them on their surfaces, and prompt other immune cells to mount an attack on pathogens. A subset of these B cells target antigens that are present from our own bodies called self-antigens, but these cells remain in a dormant state.

This new study finds that in lupus patients, nearly 1 in 400 B cells are infected by EBV (in contrast, just 1 in 10,000 B cells are infected in healthy people). In these cells, the virus produces a protein that activates a cascade of gene expression within the B cell that leads the cell to become inflammatory. These inflammatory B cells also activate self-reactive T cells, which stimulate the immune response against components of the cell nucleus. The result: lupus.

This study is broadly important because it’s possible that EBV reprograms autoreactive B cells in other autoimmune diseases. Understanding how this process works in a variety of diseases could help researchers get closer to therapeutics to block this cascade of events after EBV infection.

Citation

Younis, S., et al. (2025). Epstein-Barr virus reprograms autoreactive B cells as antigen-presenting cells in systemic lupus erythematosus. Science Translational Medicine, 17(824), eady0210. https://doi.org/10.1126/scitranslmed.ady0210