Regulation of expression of the interleukin-2 receptor alpha chain (CD25) in human tonsillar B lymphocytes

Pringle, Heather Margaret (1997) Regulation of expression of the interleukin-2 receptor alpha chain (CD25) in human tonsillar B lymphocytes. PhD thesis, University of Glasgow.

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Abstract

The Interleukin-2 Receptor α chain (IL-2Rα or CD25) plays an important role in B cell activation since it allows formation of the high affinity IL-2 Receptor and thus permits the B cell to respond to physiological concentrations of IL-2. IL-4 appears to be the sole cytokine which can induce IL-2Rα in human tonsillar B cells. In addition, polyvalent anti-lmmunoglobulin antibodies and anti-CD40 antibodies can cause up-regulation of IL- 2Rα (Burlinson et al 1995). However, although anti-lg, anti-CD40 and IL-4 can increase IL-2Rα expression, this elevation in IL-2Rα levels does not necessarily facilitate subsequent B cell proliferation in the presence of IL-2. Of the three, only anti-Ig antibodies, in combination with IL-2, could cause resting B cells to proliferate to a significant level. Stimulation of human tonsillar B cells with polyvalent anti-lg antibodies resulted in more than 80% of them acquiring an IL-2Rα -positive phenotype. IL-2Rα expression on different subsets of B cells present within the tonsillar population was studied by stimulating the cells with isotype-specific antibodies; anti-μ, anti-δ or anti-γ antibodies. Low concentrations of anti-μ antibodies up-regulated expression of IL-2Rα as did all concentrations of anti-γ antibodies. However, high doses of anti-μ antibodies and any dose of anti-δ antibodies failed to up-regulate IL-2Rα. It is possible that the failure of B cells to respond to high doses of anti-μ antibodies or to anti-δ antibodies by increasing IL-2Rα expression may cause these cells to become tolerised and thus prevent them from causing an auto-immune response. Expression of IL-2Rα on the cell surface can be related to events taking place at the promoter region of the IL-2Rα gene. There are at least three positive regulatory regions (PRRI-PRRIII) and two negative regulatory regions (NRE I and NRE II) within the promoter region and we chose to study PRR, and NREI because these regions are believed to be involved in the induction of IL-2Rα. It was found that an, as yet, unidentified protein, NRE-BP, which binds to NRE I plays a major role in controlling IL- 2Rα transcription when cells are stimulated via their sIgM receptors. NRE-BP appears to be involved in the silencing of the IL-2Rα gene and remains bound to the promoter when the B cells are stimulated with high concentrations of anti-μ antibodies. At low concentration of anti-μ antibodies, binding of NRE-BP to NRE I is attenuated. Although anti-γ antibodies up-regulate expression of IL-2Rα on the cell surface, anti-γ antibodies have no effect on the binding of NRE-BP to the promoter. Previous studies have discovered differences in signalling through the sIgM and slgG complexes. Now we have determined that sIgM and sIgG appear to act differently in the regulation of IL-2Rα and that the binding of NRE-BP to NRE I is important in this variation.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Colleges/Schools: College of Medical Veterinary and Life Sciences
Supervisor's Name: Cushley, Dr. Bill
Date of Award: 1997
Depositing User: Mrs Monika Milewska-Fiertek
Unique ID: glathesis:1997-38915
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 09 Nov 2018 10:01
Last Modified: 09 Nov 2018 10:01
URI: http://theses.gla.ac.uk/id/eprint/38915
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