Influenza virus-induced type I interferon leads to polyclonal B-cell activation but does not break down B-cell tolerance.
The link between infection and autoimmunity is not yet well understood. This study was designed to evaluate if an acute viral infection known to induce type I interferon production, like influenza, can by itself be responsible for the breakdown of immune tolerance and for autoimmunity. We first tested the effects of influenza virus on B cells in vitro. We then infected different transgenic mice expressing human rheumatoid factors (RF) in the absence or in the constitutive presence of the autoantigen (human immunoglobulin G [IgG]) and young lupus-prone mice [(NZB x NZW)F(1)] with influenza virus and looked for B-cell activation. In vitro, the virus induces B-cell activation through type I interferon production by non-B cells but does not directly stimulate purified B cells. In vivo, both RF and non-RF B cells were activated in an autoantigen-independent manner. This activation was abortive since IgM and IgM-RF production levels were not increased in infected mice compared to uninfected controls, whether or not anti-influenza virus human IgG was detected and even after viral rechallenge. As in RF transgenic mice, acute viral infection of (NZB x NZW)F(1) mice induced only an abortive activation of B cells and no increase in autoantibody production compared to uninfected animals. Taken together, these experiments show that virus-induced acute type I interferon production is not able by itself to break down B-cell tolerance in both normal and autoimmune genetic backgrounds.
Woods
Anne
A
INSERM U737, Université Louis Pasteur, Hôpitaux universitaires de Strasbourg, Strasbourg, France.
Monneaux
Fanny
F
Soulas-Sprauel
Pauline
P
Muller
Sylviane
S
Martin
Thierry
T
Korganow
Anne-Sophie
AS
Pasquali
Jean-Louis
JL
D000818:Animals; D000917:Antibody Formation; D001323:Autoantibodies / Q000378:metabolism; D001324:Autoantigens / Q000276:immunology; D015551:Autoimmunity / Q000235:genetics; D001402:B-Lymphocytes / Q000276:immunology* / Q000821:virology; D006801:Humans; D007108:Immune Tolerance; D007075:Immunoglobulin M / Q000276:immunology; D009980:Influenza A virus / Q000276:immunology*; D007370:Interferon Type I / Q000378:metabolism*; D008213:Lymphocyte Activation; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D012217:Rheumatoid Factor / Q000235:genetics
D001323:Autoantibodies; D001324:Autoantigens; D007075:Immunoglobulin M; D007370:Interferon Type I; D012217:Rheumatoid Factor