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Identifier 000382537
Title Study of the expression and function of negative immunomodulatory receptors of B lymphocytes in healthy controls and patients with systemic lupus erythematosus
Alternative Title Μελέτη της έκφρασης και της λειτουργίας αρνητικών ανοσορρυθμιστικών υποδοχέων των Β λεμφοκυττάρων σε υγιείς και ασθενείς με συστηματικό ερυθηματώδη λύκο
Author Ζαμπουλάκη, Αμαλία Γ.
Thesis advisor Μπερτσιάς, Γεώργιος
Reviewer Σιδηρόπουλος, Πρόδρομος
Τσατσάνης, Χρήστος
Abstract Systemic Lupus Erythematosus (SLE) is a systemic autoimmune disorder characterized by the presence of high-titer autoantibodies produced by long-lived plasma cells. Evidence from in vivo and in vitro studies have established activated B cells as an important component of its pathogenesis. Optimal B cell activation and differentiation requires convergent signals from the B cell receptor (BcR), Toll-like receptors (TLRs) as well as costimulatory molecules, whereas B cells can also be influenced by inhibitory immunoreceptors, such as B and T lymphocyte Attenuator (BTLA), Programmed cell death protein 1 (PD-1) and Programmed cell death 1 ligand 1 (PD-L1). This study aimed at investigating the expression and function of the coinhibitory receptors BTLA, PD-1 and PD-L1 in B cells from healthy donors and active SLE patients. BTLA, PD-1 and PD-L1 expression was examined by flow cytometry in peripheral blood naïve (CD19+IgD+CD27-), transitional (CD19+IgD+CD27+), memory (CD19+IgD-CD27+) and plasma B cells (CD19+IgD-CD27hi) at basal state and in purified peripheral blood CD19+ B cells following stimulation. BTLA ligand, HVEM (Herpes Virus Entry Mediator), expression was also considered in peripheral blood CD4+ T cells. Activation, differentiation, proliferation and IL-6 production of B cells were examined in the presence or absence of the BTLA ligand, HVEM. Analysis resulted in differential baseline expression of all three receptors studied in B cell subsets both in healthy donors and in SLE patients. HVEM levels were found to be significantly increased in SLE CD4+ T cells. BcR activation enhanced the expression all three receptors in normal B-cells; addition of CpG-ODN (TLR9 ligand) further induced PD-1 and PD-L1 –but not BTLA– expression, whereas addition of the cytokines IL-4, IL-10 or IL-21 reduced PD-1 and BTLA levels. In vitro cross linking of BTLA with HVEM resulted in decreased expression of activation markers CD80/CD86 and differentiation, in attenuation of B cell proliferation, although it had a differential effect on IL-6 production in B cells from SLE patients compared to healthy controls. In conclusion, these data demonstrate a different pattern of expression of BTLA, PD-1 and PD-L1 among B cell subsets and upon treatment with stimuli, with important implications for the modulation of B cell activation and differentiation. 14 Aberrancies in the expression and function of coinhibitory receptors in B cells could contribute to enhanced autoantibody-forming capacity and disease pathogenesis.
Language English
Subject B lymphocytes
BTLA
HVEM
Negative immunomodullatory receptors
PD-1
PD-L1
Systemic lupus erythematosus
Αρνητικοί ανοσορρυθμιστικοί υποδοχείς
Βλεμφοκύτταρα
Συστηματικός ερυθηματώδης λύκος
Issue date 2013-07-16
Collection   School/Department--School of Medicine--Department of Medicine--Post-graduate theses
  Type of Work--Post-graduate theses
Permanent Link https://elocus.lib.uoc.gr//dlib/0/f/a/metadata-dlib-1392024084-137236-8058.tkl Bookmark and Share
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