4.7 Article

Impact of myelin-specific antigen presenting B cells on T cell activation in multiple sclerosis

Journal

CLINICAL IMMUNOLOGY
Volume 128, Issue 3, Pages 382-391

Publisher

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.clim.2008.05.002

Keywords

autoimmunity; B cells; multiple sclerosis; antigen presentation

Categories

Funding

  1. Teva Pharmaceuticals [700357]
  2. Howson Funds (NLM)
  3. National Institute of Allergy and Immunology NRSA [T32 A1005284-28]

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The rote of B cells in the pathogenesis of Multiple Sclerosis (MS) is incompletely understood. Here we define a possible role for B cells as myelin-specific antigen presenting cells (B-APCs) in MS. Peripheral blood B cells (PBBC) isolated from both MS patients and healthy controls (HC) were activated in vitro with either CD40L/IL-4 or a Class B CpG oligodeoxynucleotide (CpG CDN)/IL-2. Both activation techniques induced PBBCs to upregulate CD80 and HLA-DR, rendering them more efficient APCs than resting 8 cells. Although the CD40L/IL-4 B-APCs were highly effective in eliciting CNS-antigen specific proliferation by autologous T-cells, CpG ODN/IL-2 stimulated B cells were not. Furthermore, CD40L/IL-4 B-APC induced responses by autologous CD4(+) T cells were susceptible to blocking with anti-HLA-DR antibody, suggesting that T cell responses were specific for antigen presentation by B-APC. CNS-antigen specific CD8(+) T cell proliferation was also blocked by HLA-DR, suggesting that CD8(+) proliferation is in part dependent on CD4(+) help. (C) 2008 Elsevier Inc. All rights reserved.

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