Serveur des thèses de l'Université de Strasbourg

Autoimmunity and infection : experimental approachs of the mechanisms of B cell tolerance breakdown

WOODS, Anne (2007) Autoimmunity and infection : experimental approachs of the mechanisms of B cell tolerance breakdown. Thèses de doctorat, Université Louis Pasteur.

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Abstract

Autoimmune diseases are associated with genetic and environmental factors. Among the latter, infections have been particularly implicated. However, the mecanisms of such an association between infections and autoimmune diseases are still unknown. We have tried to understand those mecanisms by using transgenic mouse models expressing chimeric rheumatoid factors (RF) in the presence or in the absence of their autoantigen (human IgG). In these models, RF B cells are ignorant towards their autoantigen. However, infection of RF trangenic mice with Borrelia burgdorferi (Bb) breaks this state of tolerance thanks to the formation of Bb/anti-Bb human IgG immune complexes that induce a synergic signal between the BCR and a receptor recognising Bb antigens (probably a Toll-like receptor, TLR). This tolerance breakdown needs T cell help.On the other hand, infection with influenza virus does not break RF B cell tolerance in our tg model although this infection is able to induce type I IFN production, otherwise often associated with autoimmune diseases, and even when the transgene is expressend on an autoimmune background, NZBxNZW(F1).Bb infection induces a polyclonal B cell activation. Ce phenomenon is not well known, it has consequences on the immune response against infections and on the production of potentially harmfull autoantibodies. The infection of MyD88 deficient mice (considered at first to understand the role of TLR in the RF B cell tolerance breakdown) showed that this protein is important for polyclonal B cell activation. MyD88 inhibits the development of a Th2 immune response, thus probably preventing an increased production of IL-4 that can directly and excessively activate B cells.

Item Type:Thesis
Discipline de la thèse / mémoire / rapport :Sciences du vivant. Aspects moléculaires et cellulaires de la biologie
Uncontrolled Keywords:B cell tolerance, rheumatoid factors, transgenic mouse models, tolerance breakdown, infection, TLR, MyD88
Subjects:UNERA Classification UNERA > ACT Domaine d'activité UNERA > ACT-5 Santé, industrie du médicament, cosmétique
CL Classification > DDC Dewey Decimal Classification > 500 Sciences de la nature et mathématiques > 570 Sciences de la vie. Biologie. Biochimie > 571 Physiologie et sujets voisins > 571.9 Pathologie
Classification Thèses Unistra > Santé > Sciences de la vie, biologie, biochimie > 570 Sciences de la vie. Biologie. Biochimie > 571 Physiologie et sujets voisins > 571.9 Pathologie

UNERA Classification UNERA > DISC Discipline UNERA > DISC-16 Sciences de la vie et de la santé, psychologie
CL Classification > DDC Dewey Decimal Classification > 600 Technologie (sciences appliquées) > 610 Médecine et santé > 616 Maladies
Classification Thèses Unistra > Santé > Médecine et odontologie > 610 Médecine et santé > 616 Maladies
ID Code:1446
Deposited On:15 April 2008

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