Autoantigen, innate immunity, and T cells cooperate to break B cell tolerance during bacterial infection.
Autoantibody production during infections is considered to result from nonspecific activation of low-affinity autoreactive B cells. Whether this can lead to autoimmune disease remains uncertain. We show that chronic infection by Borrelia burgdorferi of Tg animals expressing human rheumatoid factor (RF) B cells (of low or intermediate affinities) in the absence or in the constitutive presence of the autoantigen (represented here by chimeric IgG with human constant region) breaks their state of immunological ignorance, leading to the production of RFs. Surprisingly, this production was more pronounced in intermediate-affinity RF Tg mice co-expressing the autoantigen. This overproduction was mediated by immune complexes and involved synergistic signaling between the B cell receptor and Toll-like receptors and T cell help. These findings indicate that chronic infection can activate autoreactive B cells with significant affinity and creates conditions that can drive them to differentiate into memory cells. Such cells may have some physiological yet undetermined role, but in autoimmune-prone individuals, this scenario may initiate autoimmunity.
Soulas
Pauline
P
Laboratoire d'Immunopathologie, INSERM U737, Centre de Recherche d'Immunologie et d'Hématologie, Hôpital Civil, Strasbourg Cedex, France.
Woods
Anne
A
Jaulhac
Benoit
B
Knapp
Anne-Marie
AM
Pasquali
Jean-Louis
JL
Martin
Thierry
T
Korganow
Anne-Sophie
AS
D000818:Animals; D001324:Autoantigens / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D025065:Borrelia burgdorferi / Q000276:immunology*; D002908:Chronic Disease; D007108:Immune Tolerance; D008193:Lyme Disease / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D011947:Receptors, Antigen, B-Cell / Q000276:immunology; D011956:Receptors, Cell Surface / Q000276:immunology; D012217:Rheumatoid Factor / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D051193:Toll-Like Receptors
D001324:Autoantigens; D008562:Membrane Glycoproteins; D011947:Receptors, Antigen, B-Cell; D011956:Receptors, Cell Surface; D051193:Toll-Like Receptors; D012217:Rheumatoid Factor