Objective: One of the most devastating complications after organ transplantation is EBV-related lymphoproliferation. This condition is predominantly a B-cell disorder that is often associated with antecedent elevation of Epstein-Barr virus (EBV) loads. However, there is no consistent relationship between elevated EBV loads and the risk of progression to post-transplant lymphoproliferative disorder (PTLD). We hypothesized that aspects of the virus-host interaction could be measured to help predict progression to PTLD in settings where viral loads are elevated. Thus, the objective of this study was to examine differentially expressed host B cell-associated genes and their interaction patterns in different EBV viral load settings after pediatric organ transplantation. Specifically, we were interested in the genes expressed in high/intermediate (HI) versus low/undetectable (LU) viral load states. Methods: Gene expression was measured by microarray analysis of RNA from CD19+ B lymphocytes using the Human Genome U133 Plus 2.0 GeneChip. Moderated t-statistics were computed for each gene using a local pooled error (LPE) test. The false discovery rates (FDR) of the differentially expressed genes were evaluated and validated using RT-PCR. In this report, the primary focus was on comparisons between patients with HI and LU viral loads (VL). Using averagelinkage hierarchical clustering analysis, a set of genes with the largest variation, as measured by coefficient of variation, was used to explore the patterns of viral loads. Gene network analysis was also performed. Results: Among samples from 27 transplant recipients, the VL categories were: low or undetectable loads, N = 14; high or intermediate loads, N = 13. There were 7 healthy EBV-seropositive (P) and -seronegative controls (N). The median age of transplant patients was 12.1 yrs (range 1 16.9); Median time post-transplant 0.5 yr (range 0.1 3.8). Using the LPE test, we identified 54 differentially expressed genes with FDR 0.1 when HI was compared with LU. In addition to our comparisons of interest (HI vs LU), we examined other comparisons; HI vs P, LU vs P and P vs N, respectively. Altogether, these comparisons yielded 24 54 differentially expressed genes. Clustering analysis of 563 gene expressions identified 5 clusters aligned with levels of VL. Conclusion: Our results revealed a spectrum of B-cell associated genes that includes several that may be relevant to the pathogenesis of lymphoproliferation after organ transplantation. Further studies using the above methodology will shed further light on gene expression profiles in the setting of different viral load states after organ transplantation.