Epstein-Barr virus (EBV) persists in human B cells, and is occasionally reactivated.
We have reported that both healthy controls and Graves’ disease patients had EBV-infected B cells that had thyrotropin receptor antibodies (TRAbs) as their surface globulin (TRAb(+) EBV(+) cells). PBMCs containing TRAb(+) EBV(+) cells produced TRAbs by EBV-reactivation. We proposed an EBV reactivation-induced Ig production.
B cells that come into circulation from bone marrow are activated by their specific antigens and cognate T cells, and enter lymphoid tissue. Then, they form germinal centers, and finally produce high-affinity IgGs in bone marrow. However, autoreactive B cells have difficulty to encounter their specific autoantigen, and are eliminated. When EBV infect these autoreactive B cells, they can be activated by EBV-LMP1. EBV-reactivation make them produce autoantibodies.
Although the stimulating TRAbs are IgG, the TRAbs produced by EBV reactivation are IgM dominant. We cultured porcine thyroid cells with TRAbs purified from culture of TRAb(+) EBV(+) cells with compliments, and observed cytotoxicity confirmed by LDH releasing. TRAb-IgM may have the role to release thyroid antigens and contribute to thyroid autoimmunity. The relevance of EBV reactivation to Graves’ disease may have a possibility for the new therapy.