The role of B cells in the onset of the first demyelinating event of XXXX .

@entity1 @entity404 @entity1075 @entity5750 @entity7995 @entity15 @entity405
UNASSIGNED: Purpose. To evaluate the molecular pathways that operate in the early phase of acute @entity7995 by studying gene expression profiles of peripheral blood mononuclear cells (PBMCs) subpopulations including @entity1075 + B cells, @entity5750 + macrophages, @entity404 + and @entity405 + T cells. Methods. PBMC subpopulations were obtained from 11 @entity15 @entity1 within 96 hours of the acute onset of the first demyelinating event of ON and from 14 healthy subjects. Gene expression analysis was performed on samples from 6 ON @entity1 and 9 healthy subjects (Affymetrix). Data was analyzed using Partek software and most informative genes (MIGs) were defined with p<0.01 and fold change >2.0. Verification of key MIGs was done by QRT-PCR and Western blot. Functional assay to test antigen presentation ability of B cells was performed. Results. Significantly differentiating gene expression signatures consisting of 467, 55, and 55 MIGs respective of @entity1075 +, @entity5750 + and @entity404 + cells were identified between ON and healthy subjects. No MIGs was detected for @entity405 + cells. The major involvement of @entity1075 + B cells in the early stage of ON was characterized by enrichment of genes involved in activation of immune mechanisms (p=3.2*10-25 to 2.5*10-3) including cellular immune response (p=7.1*10-12), B cells cellular growth and proliferation (p=1.0*10-7), activation of immune cells trafficking pathways (p=5.4*10-15 to 2.0*10-3), and stimulation of antigen presentation (p=8.9*10-11). Conclusions. Our findings demonstrate that @entity1075 + B cells play a significant role in the pathogenesis of the first demyelinating event of acute ON and suggest their role as possible target for immunomodulation.
