From systemic T cell self-reactivity to organ-specific autoimmune disease via immunoglobulins.
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.
Korganow
A S
AS
Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, C. U. de Strasbourg, France.
Ji
H
H
Mangialaio
S
S
Duchatelle
V
V
Pelanda
R
R
Martin
T
T
Degott
C
C
Kikutani
H
H
Rajewsky
K
K
Pasquali
J L
JL
Benoist
C
C
Mathis
D
D
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*
D018985:Epitopes, B-Lymphocyte; D007136:Immunoglobulins