Naturally self-reactive B cells are poised to cross the selection barrier into autoimmune germinal centers - PubMed
7 hours ago
- #B cells
- #autoimmunity
- #germinal centers
- Approximately 20% of circulating B cells are self-reactive.
- The study used the 564Igi mouse model to explore whether autoreactive B cells expand when immune tolerance is breached.
- Naive B cells with human-like CDRH3 diversity were introduced, focusing on two alleles of the IGHV1-69 gene (F54 and L54 variants).
- L54 variant B cells, which confer autoreactivity, were selectively retained in autoimmune germinal centers in the 564Igi model but not in wild-type mice.
- The L54 variant is also found in human ancestral populations, including Neanderthals and Denisovans, suggesting an ancient origin for self-reactive B cell pools.
- Findings indicate that self-reactive B cells are primed to expand in autoimmune conditions, contributing to autoimmunity.