Abstract
Burkitt lymphoma (BL) is characterized by elevated levels of the enzyme activation-induced cytidine deaminase (AID), an enzyme critical for MYC translocation that is the hallmark of BL. Both EBV and Plasmodium falciparum malaria are cofactors in the etiology of BL. However, how these 2 pathogens drive BL pathogenesis is not yet understood. In this study, we tested the hypothesis that P. falciparum and EBV synergize to induce dysregulated expression of AID. Using flow cytometry, intracellular AID expression was measured in PBMCs from a cohort of children from Western Kenya with uncomplicated malaria and community controls. Children with uncomplicated malaria had elevated levels of CD19+ AID+ B cells compared to controls. This high level of AID was sustained up to 8 weeks after parasite clearance. Using ImageStream flow cytometry, we found that 52% of AID was localized in the nucleus of CD19+ B cells in children with malaria. To test whether EBV and P. falciparum synergized to drive the expression of AID, we stimulated CD19+ B cells with EBV, CpG (to mimic P. falciparum DNA), or BAFF (induced during P. falciparum infection), or as a combination. Individually, EBV, BAFF and CpG induced AID expression. However, when combined, there was a significant increase of ∼30% in the frequency of CD19+AID+ cells above cells treated with EBV, BAFF, or CpG individually. Collectively, these data suggest that P. falciparum malaria and EBV coinfection result in sustained AID expression, potentially influencing the MYC translocation that is characteristic of BL.