Germinal-centre and extrafollicular B cell pathways in systemic lupus erythematosus - PubMed
3 hours ago
- #B Cell Pathways
- #Autoimmunity
- #Systemic Lupus Erythematosus
- Autoantibody flares are key drivers of pathology in systemic lupus erythematosus (SLE), emphasizing B cells' central role in chronic autoimmunity.
- Layered tolerance checkpoints normally suppress autoreactive naive B cells, but autoimmune-prone environments can lower these thresholds, making them more sensitive to aberrant activation signals.
- Cytokines and microenvironmental signals direct autoreactive B cells toward germinal-center or extrafollicular differentiation pathways, which are complementary sources of autoreactive effector cells.
- Germinal centers support autoreactive B cell entry, selection, and diversification with T cell help, while extrafollicular pathways require less T cell help and rely more on complement and TLR signaling.
- Research is needed on the origin, development, longevity, and tissue dynamics of autoreactive memory B cells as chronic autoantibody sources, and precision therapies targeting pathogenic subsets are a key challenge.