Dissecting the contribution of B cells in an experimental model of rheumatoid arthritis

Conigliaro, Paola (2014) Dissecting the contribution of B cells in an experimental model of rheumatoid arthritis. PhD thesis, University of Glasgow.

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Abstract

Rheumatoid Arthritis (RA) is a chronic systemic autoimmune disease characterised by extensive synovitis resulting in cartilage and bone erosions. Both the innate and adaptive immune pathways contribute to the initiation and the maintenance of the disease. Understanding the role of these pathways is central to develop new therapeutics. We have developed a murine model of RA where ovalbumin (OVA) specific Th1 cells induced a breach of self-tolerance and a transient monoarthritis. This thesis aimed firstly to create a model of chronic autoimmune polyarthritis and then to investigate the contribution of B cells and innate inflammation to the induction of arthritis. Relapse of arthritis was associated with the nature of the antigen (OVA) employed and the route of administration. The analysis of collagen specific B cell response revealed that anti-type II collagen antibodies titres rise during the induction of the relapse of arthritis and that they were directed against the epitope U1. Although typical RA autoantibodies were detected in OVA-mediated arthritis, a mild arthritis could be elicited in absence of antigen presenting B cells and in complete absence of mature B cells. B cells were not necessary in the induction of pathology even though their presence was associated with a higher joint histology score. Finally, this thesis describes that an innate inflammatory stimulus, such as LPS, elicited joint pathology but was insufficient to breach B and T self-tolerance. On the contrary, antigen-specific T cell activation led to arthritis and the production of several autoantibodies typical of RA. The relapse and spread of arthritis developed in this thesis provides a useful tool to investigate the contribution of the innate and adaptive immune pathways in the development of autoreactive responses. A better understanding of these mechanisms will hopefully help to design new therapeutic intervention aiming to re-establish immunological tolerance.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Keywords: Rheumatoid Arthritis, B cells, experimental model, CIA
Subjects: R Medicine > R Medicine (General)
R Medicine > RB Pathology
Colleges/Schools: College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation > Immunology
Funder's Name: UNSPECIFIED
Supervisor's Name: McInnes, Professor Ian
Date of Award: 2014
Depositing User: Dr Paola Conigliaro
Unique ID: glathesis:2014-6209
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 20 Mar 2015 15:50
Last Modified: 24 Mar 2015 08:37
URI: http://theses.gla.ac.uk/id/eprint/6209

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