Objective:This study aimed to comprehensively assess Epstein-Barr virus (EBV)-induced methylation alterations of B cell across whole genome.Methods:We compared DNA methylation patts of primary B cells and corresponding lymphoblastoid cell lines (LCLs) from eight participants.The genome-wide DNA methylation profiles were compared at over 850,000 genome-wide methylation sites.Results:DNA methylation analysis revealed 87,732 differentially methylated CpG sites,representing approximately 12.41％ of all sites in LCLs compared to primary B cells.The hypermethylated and hypomethylated CpG sites were about 22.75％ or 77.25％,respectively.Only 0.8％ of hypomethylated sites and 4.5％ of hypermethylated sites were located in CpG islands,whereas 8.0％ of hypomethylated sites and 16.3％ of hypermethylated sites were located in shore (N_shore and S_shore).Using principal component analysis of the DNA methylation profiles,primary B cells and LCLs could be accurately predicted.Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of differently methylated genes revealed that most of the top GO biological processes were related to cell activation and immune response,and some top enrichment pathways were related with activation and malignant transformation of human B cells.Conclusions:Our study demonstrated genome-wide DNA methylation variations between primary B cells and corresponding LCLs,which might yield new insight on the methylation mechanism of EBV-induced immortalization.