Infection of autoreactive B lymphocytes with EBV, causing chronic autoimmune diseases.
I hypothesize that human chronic autoimmune diseases are based on infection of autoreactive B lymphocytes by Epstein-Barr virus (EBV), in the following proposed scenario. During primary infection, autoreactive B cells are infected by EBV, proliferate and become latently infected memory B cells, which are resistant to the apoptosis that occurs during normal B-cell homeostasis because they express virus-encoded anti-apoptotic molecules. Genetic susceptibility to the effects of B-cell infection by EBV leads to an increased number of latently infected autoreactive memory B cells, which lodge in organs where their target antigen is expressed, and act there as antigen-presenting cells. When CD4(+) T cells that recognize antigens within the target organ are activated in lymphoid organs by cross-reactivity with infectious agents, they migrate to the target organ but fail to undergo activation-induced apoptosis because they receive a co-stimulatory survival signal from the infected B cells. The autoreactive T cells proliferate and produce cytokines, which recruit other inflammatory cells, with resultant target organ damage and chronic autoimmune disease.
Department of Medicine, The University of Queensland, Clinical Sciences Building, Royal Brisbane Hospital, 4029, Herston, Queensland, Australia. m.hawes@mailbox.uq.edu.au
Michael P
MP
Pender
D001327:Autoimmune Diseases / Q000209:etiology* / Q000276:immunology / Q000821:virology; D015551:Autoimmunity; D001402:B-Lymphocytes / Q000276:immunology*; D020031:Epstein-Barr Virus Infections / Q000209:etiology / Q000276:immunology*; D005802:Genes, MHC Class II; D004854:Herpesvirus 4, Human / Q000472:pathogenicity*; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000209:etiology / Q000276:immunology / Q000821:virology; D018448:Models, Immunological; D009103:Multiple Sclerosis / Q000209:etiology / Q000276:immunology / Q000821:virology; D013601:T-Lymphocytes / Q000276:immunology