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Cellular and molecular dynamics of ectopic germinal centre formation in rheumatoid arthritis

Objective

B lymphocytes are key effector cells in adaptive immune responses against foreign antigens, by producing antibodies and processing and presenting the antigen to T lymphocytes. In healthy individuals B lymphocyte differentiation and maturation takes place in the germinal centres of peripheral lymphoid organs.

However, in chronic inflammatory autoimmune diseases (e.g. rheumatoid arthritis, Sjogren syndrome) ectopic germinal centres develop at the sites of inflammation, allowing an (auto)antigen dependent immune response, thus perpetuating the inflammation, and eventually breaking the tolerance mechanisms.

Therefore, using both mathematical and animal models, the aim of the present proposal is to clarify the genetic, molecular and cellular mechanisms underlying abnormal B lymphocyte development and function and the formation and maintenance of ectopic germinal centres in autoimmune diseases.

Call for proposal

FP6-2004-MOBILITY-5
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Coordinator

FUNDACAO CALOUSTE GULBENKIAN
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Avenida de Berna, 45-A
LISBOA
Portugal

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