Impact of myelin-specific antigen presenting B cells on T cell activation in multiple sclerosis.
The role 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 ODN)/IL-2. Both activation techniques induced PBBCs to upregulate CD80 and HLA-DR, rendering them more efficient APCs than resting B 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.
Harp
Christopher T
CT
Department of Neurology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Lovett-Racke
Amy E
AE
Racke
Michael K
MK
Frohman
Elliot M
EM
Monson
Nancy L
NL
D000938:Antigen-Presenting Cells / Q000276:immunology*; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D018122:B7-1 Antigen / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D023201:CD40 Ligand / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D006684:HLA-DR Antigens / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007376:Interleukin-2 / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D008213:Lymphocyte Activation; D009103:Multiple Sclerosis / Q000276:immunology*; D009186:Myelin Sheath / Q000276:immunology*; D009838:Oligodeoxyribonucleotides / Q000276:immunology; D015854:Up-Regulation
D018122:B7-1 Antigen; C408982:CPG-oligonucleotide; D006684:HLA-DR Antigens; D007376:Interleukin-2; D009838:Oligodeoxyribonucleotides; D023201:CD40 Ligand; D015847:Interleukin-4