Infection of autoreactive B lymphocytes with EBV, causing chronic autoimmune diseases

Trends Immunol. 2003 Nov;24(11):584-8. doi: 10.1016/


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Autoimmune Diseases / etiology*
  • Autoimmune Diseases / immunology
  • Autoimmune Diseases / virology
  • Autoimmunity
  • B-Lymphocytes / immunology*
  • Epstein-Barr Virus Infections / etiology
  • Epstein-Barr Virus Infections / immunology*
  • Genes, MHC Class II
  • Herpesvirus 4, Human / pathogenicity*
  • Humans
  • Lupus Erythematosus, Systemic / etiology
  • Lupus Erythematosus, Systemic / immunology
  • Lupus Erythematosus, Systemic / virology
  • Models, Immunological
  • Multiple Sclerosis / etiology
  • Multiple Sclerosis / immunology
  • Multiple Sclerosis / virology
  • T-Lymphocytes / immunology