Article

Intravenous transfusion of BCR-activated B cells protects NOD mice from type 1 diabetes in an IL-10-dependent manner.

Laboratory of Autoimmune Diabetes, Robarts Research Institute, University of Western Ontario, London, ON, Canada.
The Journal of Immunology (Impact Factor: 5.36). 01/2008; 179(11):7225-32. DOI: 10.4049/jimmunol.179.11.7225
Source: PubMed

ABSTRACT Although B cells play a pathogenic role in the initiation of type 1 diabetes (T1D) in NOD mice, it is not known whether activated B cells can maintain tolerance and transfer protection from T1D. In this study, we demonstrate that i.v. transfusion of BCR-stimulated NOD spleen B cells into NOD mice starting at 5-6 wk of age both delays onset and reduces the incidence of T1D, whereas treatment initiated at 9 wk of age only delays onset of T1D. This BCR-activated B cell-induced protection from T1D requires IL-10 production by B cells, as transfusion of activated B cells from NOD.IL-10(-/-) mice does not confer protection from T1D. Consistent with this result, severe insulitis was observed in the islets of NOD recipients of transfused NOD.IL-10(-/-) BCR-stimulated B cells but not in the islets of NOD recipients of transfused BCR-stimulated NOD B cells. The therapeutic effect of transfused activated NOD B cells correlates closely with the observed decreased islet inflammation, reduced IFN-gamma production and increased production of IL-4 and IL-10 by splenocytes and CD4(+) T cells from NOD recipients of BCR-stimulated NOD B cells relative to splenocytes and CD4(+) T cells from PBS-treated control NOD mice. Our data demonstrate that transfused BCR-stimulated B cells can maintain long-term tolerance and protect NOD mice from T1D by an IL-10-dependent mechanism, and raise the possibility that i.v. transfusion of autologous IL-10-producing BCR-activated B cells may be used therapeutically to protect human subjects at risk for T1D.

0 Followers
 · 
139 Views
  • Source
    Frontiers in Immunology 07/2012; 3:206. DOI:10.3389/fimmu.2012.00206
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: B lymphocytes represent a major component of the immune system and their best understood effector functions are antibody production, presentation of antigens to T cells and the modulation of immune responses via cytokine production. Although most of these functions serve to amplify immune responses, B cells have also been demonstrated to downregulate inflammatory reactions and induce tolerance. As such, regulatory B (Breg) cells have been implicated in various inflammatory conditions. There is evidence for Breg cell deficiencies in human autoimmune diseases and various adoptive transfer experiments in mouse models of autoimmune and allergic conditions indicate that Breg cells are capable of suppressing disease development. In this review we endeavour to give an overview of the current knowledge about regulatory B cell immunobiology and their implications in autoimmune and allergic disorders.
    Recent Advances in Immunology to Target Cancer, Inflammation and Infections, Edited by Jagat R. Kanwar, 01/2012: chapter 9; InTech., ISBN: 978-953-51-0592-3
  • [Show abstract] [Hide abstract]
    ABSTRACT: Once considered to be predominantly a positive regulator of immune function, B cells are increasingly getting attributed with new and diversified functions. In recent years a number of reports indicate that a definite regulatory function of B cell exists. A number of B cell subsets that shares various developmental markers shown to have the ability to produce the suppressive cytokine IL-10. A particularly strong candidate with distinct IL-10 production profile is CD19hiCD1dhiCD5+ population, which constitutes about 1–2 % of splenic B cells. These B cells are also called B10 cells as they produce large amount of IL-10. Increasingly it is becoming clear that a variety of regulatory B cell population exists and expands during inflammatory condition and autoimmune disease. A detailed study of development and mechanism that governs B reg generation may provide us with valuable information for therapeutic intervention.
    06/2014; 67(1). DOI:10.1007/s12595-013-0077-0

Preview

Download
0 Downloads
Available from