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.
Holmøy
Trygve
T
Institute of Immunology, University of Oslo and Oslo University Hospital Rikshospitalet, Oslo, Norway. trygve.holmoy@rr-research.no <trygve.holmoy@rr-research.no>
Vartdal
Frode
F
Hestvik
Anne Lise
AL
Munthe
Ludvig
L
Bogen
Bjarne
B
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D002450:Cell Communication; D006801:Humans; D007130:Immunoglobulin Idiotypes / Q000276:immunology*; D007135:Immunoglobulin Variable Region / Q000276:immunology*; D009103:Multiple Sclerosis / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology
D007130:Immunoglobulin Idiotypes; D007135:Immunoglobulin Variable Region