AID expression in peripheral blood of children living in a malaria holoendemic region is associated with changes in B cell subsets and Epstein-Barr virus

• Type of Material: Article
• Authors: Joel R Wilmore, SUNY Upstate Medical University; Amolo S Asito, Kenya Medical Research Institute; Chungwen Wei, Emory University; Erwan Piriou, Kenya Medical Research Institute; P. Odada Sumba, Kenya Medical Research Institute; Ignacio Sanz, Emory University; Rosemary Rochford, SUNY Upstate Medical University
• Language: English
• Date: 2015-03-15
• Publisher: Wiley
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2014 UICC.
• Final Published Version (URL): http://dx.doi.org/10.1002/ijc.29127
• Title of Journal or Parent Work: International Journal of Cancer
• ISSN: 0020-7136
• Volume: 136
• Issue: 6
• Start Page: 1371
• End Page: 1380
• Grant/Funding Information: NIH. Grant Numbers: R01CA102667, R37AI049660, R01AI084808, P01AI078907; Alex's Lemonade Stand
• Keywords: INFECTION; DNA; Life Sciences & Biomedicine; activation induced cytidine deaminase; Science & Technology; ACTIVATION; C-MYC ONCOGENE; plasmodium; BURKITTS-LYMPHOMA; PLASMODIUM-FALCIPARUM; IN-VIVO; INDUCED CYTIDINE DEAMINASE; Epstein-Barr Virus; malaria; Oncology; GERMINAL-CENTERS; Burkitt's lymphoma; KENYA
• Research Categories: Health Sciences, General; Health Sciences, Oncology; Health Sciences, Immunology

Abstract

The development of endemic Burkitt's lymphoma (eBL) is closely associated with Epstein-Barr virus (EBV) infection and holoendemic malaria infections. The role of EBV in the development of malignancy has been studied in depth, but there is still little known about the mechanisms by which malaria affects Burkitt's lymphomagenesis. Activation induced cytidine deaminase (AID) expression is necessary for the introduction of c-myc translocations that are characteristic of BL, but a link between AID and EBV or malaria is unclear. To determine whether frequency of malaria exposure leads to increased AID expression in peripheral blood mononuclear cells (PBMC) we examined two cohorts of children in western Kenya with endemic and sporadic malaria transmission dynamics. High frequency of malaria exposure led to increased expression of AID, which coincided with decreases in the IgM+ memory B cells. In the children from the malaria endemic region, the presence of a detectible EBV viral load was associated with higher AID expression compared to children with undetectable EBV, but this effect was not seen in children with sporadic exposure to malaria. This study demonstrates that intensity of malaria transmission correlates with AID expression levels in the presence of EBV suggesting that malaria and EBV infection have a synergistic effect on the development of c-myc translocations and BL.