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.
Pender
Michael P
MP
Department of Medicine, The University of Queensland, Clinical Sciences Building, Royal Brisbane Hospital, 4029, Herston, Queensland, Australia. m.hawes@mailbox.uq.edu.au
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