UCL  IRIS
Institutional Research Information Service
UCL Logo
Please report any queries concerning the funding data grouped in the sections named "Externally Awarded" or "Internally Disbursed" (shown on the profile page) to your Research Finance Administrator. Your can find your Research Finance Administrator at https://www.ucl.ac.uk/finance/research/rs-contacts.php by entering your department
Please report any queries concerning the student data shown on the profile page to:

Email: portico-services@ucl.ac.uk

Help Desk: http://www.ucl.ac.uk/ras/portico/helpdesk
Publication Detail
Cross-talk between invariant natural killer T cells and B cells under homeostatic conditions and during inflammation
  • Publication Type:
    Thesis/Dissertation
  • Authors:
    Bosma A
  • Date awarded:
    14/05/2013
  • Supervisors:
    Mauri C,Jury EC
  • Awarding institution:
    UCL
  • Language:
    English
  • Notes:
    UCL > School of Life and Medical Sciences > Faculty of Medical Sciences > Medicine (Division of)
Abstract
B cells perform several immunological functions, including the production of antibodies, release of cytokines and presentation peptide or lipid-antigen respectively to T or invariant natural killer T (iNKT) cells. Patients with systemic lupus erythematous (SLE) display dysregulated B cell responses and reduced peripheral iNKT cell frequencies. The significance of these defects and how they relate to SLE pathogenesis remains elusive. I examined the role of B cells in the maintenance of iNKT cells in healthy individuals and SLE patients. I report that B cells are essential for iNKT cell expansion and activation in healthy individuals but fail to exert a similar effect in SLE patients. Defective B cell-mediated iNKT cell stimulation in SLE was associated with rapid internalization and reduced CD1d surface expression on SLE B cells compared to healthy B cells, a defect that could be recapitulated in healthy B cells after simultaneous stimulation with interferon-alpha and anti-immunoglobulin. Strikingly, iNKT cell number and function were restored in SLE patients responding to anti-CD20 treatment upon normalization of CD1d levels exclusively in repopulated immature B cells. Furthermore, I demonstrated that B cells are essential for the maintenance of iNKT cells during experimental arthritis. Whereas alphaGalCer treatment ameliorated arthritis in wild-type mice, alphaGalCer treatment had no effect in arthritic B cell deficient mice. Amelioration of arthritis was paralleled with the proliferation of iNKT cells and a skew towards a Th2-like cytokine milieu. Further, I show that iNKT cells are necessary for the differentiation of regulatory B cells (Bregs). Whereas WT Bregs were capable of suppressing arthritis, Bregs isolated from iNKT cell deficient mice failed to exert the same effect despite producing IL-10. Impaired Breg suppression was associated with a potential trafficking defect. These results suggest that B cell-iNKT cell cross-talk is pivotal for the maintenance of tolerance in both human and mice.
Publication data is maintained in RPS. Visit https://rps.ucl.ac.uk
 More search options
UCL Researchers
Editor
Inflammation
University College London - Gower Street - London - WC1E 6BT Tel:+44 (0)20 7679 2000

© UCL 1999–2011

Search by