EBV reprograms autoreactive anti-CNS B cells as antigen presenting cells in multiple sclerosis - PubMed
3 hours ago
- #Autoimmunity
- #Multiple Sclerosis
- #Epstein-Barr Virus
- Multiple sclerosis (MS) is a chronic autoimmune disease targeting the central nervous system (CNS).
- MS develops almost exclusively in individuals previously infected with Epstein-Barr virus (EBV).
- EBV directly infects autoreactive anti-CNS antigen B cells and reprograms them into pro-inflammatory antigen-presenting cells (APCs).
- EBV-infected B cells in MS were enriched within the CD27-CD21 low memory B-cell subset and exhibited upregulated B cell activation and APC transcriptional programs.
- Recombinant antibodies derived from MS blood and cerebrospinal fluid (CSF) EBV-infected B cells bound brain tissue and cross-bound MS-associated autoantigens and Epstein-Barr virus nuclear antigen-1 (EBNA1).
- In vitro, EBV-infected B cells functioned as APCs that stimulated T peripheral helper cells, activating EBV-infected anti-CNS antigen B cells.
- The findings support a mechanistic framework where EBV infection reprograms autoreactive B cells into APCs, driving pathogenic anti-CNS antigen T cell and EBV-B cell responses in MS.