title: From systemic T cell self-reactivity to organ-specific autoimmune disease via immunoglobulins.
abstract: Rheumatoid arthritis is a common and debilitating autoimmune disease whose cause and mechanism remain a mystery. We recently described a T cell receptor transgenic mouse model that spontaneously develops a disease with most of the clinical, histological, and immunological features of rheumatoid arthritis in humans. Disease development in K/BxN mice is initiated by systemic T cell self-reactivity; it requires T cells, as expected, but B cells are also needed, more surprisingly. Here, we have identified the role of B cells as the secretion of arthritogenic immunoglobulins. We suggest that a similar scenario may unfold in some other arthritis models and in human patients, beginning with pervasive T cell autoreactivity and ending in immunoglobulin-provoked joint destruction.
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, C. U. de Strasbourg, France.
authors.forename: A S
authors.initials: AS
authors.lastname: Korganow
authors.forename: H
authors.initials: H
authors.lastname: Ji
authors.forename: S
authors.initials: S
authors.lastname: Mangialaio
authors.forename: V
authors.initials: V
authors.lastname: Duchatelle
authors.forename: R
authors.initials: R
authors.lastname: Pelanda
authors.forename: T
authors.initials: T
authors.lastname: Martin
authors.forename: C
authors.initials: C
authors.lastname: Degott
authors.forename: H
authors.initials: H
authors.lastname: Kikutani
authors.forename: K
authors.initials: K
authors.lastname: Rajewsky
authors.forename: J L
authors.initials: JL
authors.lastname: Pasquali
authors.forename: C
authors.initials: C
authors.lastname: Benoist
authors.forename: D
authors.initials: D
authors.lastname: Mathis
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000918:Antibody Specificity / Q000235:genetics; D017951:Antigen Presentation / Q000235:genetics; D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D001402:B-Lymphocytes / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D018985:Epitopes, B-Lymphocyte / Q000235:genetics / Q000276:immunology; D006801:Humans; D007136:Immunoglobulins / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D008822:Mice, Transgenic; D009928:Organ Specificity / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D018985:Epitopes, B-Lymphocyte; D007136:Immunoglobulins