Birte Kristensen
Afdeling M – Medicinisk Endokrinologi
Det Sundhedvidenskabelig Fakultet
JB Winsløwvej 19, 3.
Odense DK-5000
Background – Human B lymphocytes are efficient at antigen presentation as well as producing
antibodies and cytokines including pro-inflammatory cytokines, such as interleukin-6 (IL-6) and tumor
necrosis factor –α (TNF-α), as well as regulatory cytokines, such as IL-10. In terms of human
autoimmune disease, B lymphocytes may either ameliorate or acerbate the condition. However, little is
known about the factors that can initiate these harmful or protective B cell responses.
B lymphocytes producing IL-10, also called regulatory B cells, have been detected after stimulation
with a strong mitogenic agent. These regulatory B cells have shown to dampen the immune response
in various animal models of autoimmune disease. In terms of autoimmune thyroid disease (AITD),
including Graves’ disease (GD) and Hashimoto’s thyroiditis (HT), it still needs to be determined
whether regulatory B cells are more scarce or dysfunctional in patients as compared to healthy
individuals. In general, it would be of great interest if these cells can be distinguished based on specific
surface markers. This would hold great therapeutic potential.
The immuno-pathology of thyroid related eye symptoms referred to as Graves' ophthalmopathy still
requires a greater understanding. Over half of GD patients develop this condition, which leads to
swelling of the eye, compromised eyesight and often cosmetic and psychological problems.
Aims –
 To understand the ability of human B cells to present antigen with special focus on AITDassociated self-antigens.
 To determine whether B cells in AITD can be subdivided into separate functional subpopulations depending on their phenotype and cytokine production.
 To better understand the role of fibroblasts/fibrocytes in GD pathogenesis.
Methods – The methods include mononuclear cell isolation along with specific cellular subset
isolation, cell culture, and in vitro stimulation with AITD-associated self-antigens. Cytokines are
measured after in vitro stimulation using Luminex technology. Flow cytometry will be used for
phenotype characterisation and cytokine expression.
Future prospects – to gain a better understanding of the antigen-presenting ability of B lymphocytes
with special focus on thyroid-related self-antigens. The insights gained from this project will hopefully
lead to greater understanding of AITD pathology, or an improvement in AITD therapy.
Annual overview –
Year 1 – All methods will be developed and improved. Peripheral blood from GD and HT patients
along with healthy controls will be collected. Thyroid self-antigens will be provided and
characterization of various cell populations will take place. This data will constitute the first article.
Year 2 – Thyroid glands will be collected and mononuclear cells will be isolated. Intra-thyroidal
lymphocytes will undergo phenotype characterization. This data will constitute the second article.
Year 3 – Cultivation of fibrocytes along with their phenotype characterization and their ability to
present thyroid associated auto-antigens.