title: Role of type I interferons in the activation of autoreactive B cells.
abstract: Type I interferons (IFNs) are a family of cytokines involved in the defense against viral infections that play a key role in the activation of both the innate and adaptive immune system. IFNs both directly and indirectly enhance the capacity of B lymphocytes to respond to viral challenge and produce cytotoxic and neutralizing antibodies. However, prolonged type I IFN exposure is not always beneficial to the host. If not regulated properly IFN can drive autoantibody production as well as other parameters of systemic autoimmune disease. Type I IFNs impact B-cell function through a variety of mechanisms, including effects on receptor engagement, Toll-like receptor expression, cell migration, antigen presentation, cytokine responsiveness, cytokine production, survival, differentiation and class-switch recombination. Type I IFNs are also cytotoxic for a variety of cell types and thereby contribute to the accumulation of cell debris that serves as a potential source for autoantigens. Type I IFN engagement of a variety of accessory cells further promotes B-cell survival and activation, as exemplified by the capacity of type I IFNs to increase the level of B-cell survival factors, such as B lymphocyte stimulator, produced by dendritic cells. Therefore, it is not surprising that the loss of expression of the type I IFN receptor can have dramatic effects on the production of autoantibodies and on the clinical features of systemic autoimmune diseases such as systemic lupus erythematosus.
authors.affiliation: Department of Medicine, University of Massachusetts School of Medicine, Worcester, MA 01605, USA.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Kiefer
authors.forename: Michael A
authors.initials: MA
authors.lastname: Oropallo
authors.forename: Michael P
authors.initials: MP
authors.lastname: Cancro
authors.forename: Ann
authors.initials: A
authors.lastname: Marshak-Rothstein
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology*; D015551:Autoimmunity; D053264:B-Cell Activating Factor / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D002470:Cell Survival / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D007370:Interferon Type I / Q000276:immunology*; D008213:Lymphocyte Activation; D014777:Virus Diseases / Q000276:immunology*
chemical_list: D053264:B-Cell Activating Factor; D007370:Interferon Type I