The idiotype connection: linking infection and multiple sclerosis

B cells present idiotopes (Id) from their B cell receptor to Id-specific CD4+ T cells. Chronic Id-driven T-B cell collaboration can cause autoimmune disease in mice. We propose that Id-driven T-B cell collaboration mediates the development of multiple sclerosis by perpetuating immune responses initiated against infectious agents. During germinal centre reactions, B cells express a multitude of mutated Ids. While most mutations lead to decreased affinity and deletion of the B cell, some B cells could be rescued by Id-specific T cells. Such Id-connected T-B cell pairs might initiate inflammatory foci in the central nervous system. This model may explain the intrathecal synthesis of low-avidity IgG against viruses, and the synthesis of oligoclonal IgG with unknown specificity in multiple sclerosis.