title: 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.
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.
authors.affiliation: Center for Global Health and Translational Science, Department of Microbiology and Immunology, State University of New York Upstate Medical University, Syracuse, NY.
authors.forename: Joel R
authors.initials: JR
authors.lastname: Wilmore
authors.forename: Amolo S
authors.initials: AS
authors.lastname: Asito
authors.forename: Chungwen
authors.initials: C
authors.lastname: Wei
authors.forename: Erwan
authors.initials: E
authors.lastname: Piriou
authors.forename: P Odada
authors.initials: PO
authors.lastname: Sumba
authors.forename: Iñaki
authors.initials: I
authors.lastname: Sanz
authors.forename: Rosemary
authors.initials: R
authors.lastname: Rochford
mesh_terms: D016175:B-Lymphocyte Subsets / Q000276:immunology*; D001402:B-Lymphocytes / Q000201:enzymology*; D002051:Burkitt Lymphoma / Q000209:etiology* / Q000276:immunology; D002675:Child, Preschool; D003564:Cytidine Deaminase / Q000097:blood / Q000235:genetics / Q000502:physiology*; D019353:Endemic Diseases; D004854:Herpesvirus 4, Human / Q000302:isolation & purification*; D006801:Humans; D007156:Immunologic Memory; D007223:Infant; D008288:Malaria / Q000150:complications* / Q000453:epidemiology; D012333:RNA, Messenger / Q000032:analysis; D019562:Viral Load; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
chemical_list: D012333:RNA, Messenger; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase
keywords: Burkitt's lymphoma; Epstein-Barr Virus; activation induced cytidine deaminase; malaria; plasmodium
references.citation: J Immunol. 2009 Aug 1;183(3):2176-82
references.pmid: 19592645
references.citation: Infect Immun. 2004 Sep;72(9):5412-8
references.pmid: 15322039
references.citation: Proc Natl Acad Sci U S A. 2003 Nov 25;100(24):14269-74
references.pmid: 14603034
references.citation: Lancet. 2011 May 21;377(9779):1770-6
references.pmid: 21514658
references.citation: Malar J. 2011 Dec 13;10:362
references.pmid: 22166136
references.citation: J Exp Med. 2009 Nov 23;206(12):2659-69
references.pmid: 19917772
references.citation: Blood. 2006 Dec 1;108(12):3859-64
references.pmid: 16882707
references.citation: Blood. 2009 Jul 16;114(3):547-54
references.pmid: 19478044
references.citation: J Infect Dis. 2007 Mar 15;195(6):799-808
references.pmid: 17299709
references.citation: J Infect Dis. 2012 Mar 15;205(6):906-13
references.pmid: 22301635
references.citation: Cell. 1987 Apr 24;49(2):161-70
references.pmid: 3032447
references.citation: Cell. 2004 Aug 20;118(4):431-8
references.pmid: 15315756
references.citation: Proc Natl Acad Sci U S A. 2007 Feb 6;104(6):1919-24
references.pmid: 17261807
references.citation: Trop Med Int Health. 2007 Aug;12(8):936-43
references.pmid: 17697088
references.citation: J Immunol. 2004 Oct 1;173(7):4479-91
references.pmid: 15383579
references.citation: J Infect Dis. 2005 Apr 15;191(8):1233-8
references.pmid: 15776368
references.citation: Blood. 2008 Feb 1;111(3):1448-55
references.pmid: 18006702
references.citation: Int J Cancer. 2007 Jan 1;120(1):121-7
references.pmid: 17019706
references.citation: Cell. 2008 Dec 12;135(6):1028-38
references.pmid: 19070574
references.citation: AIDS. 2007 Nov 12;21(17):2265-70
references.pmid: 18090274
references.citation: PLoS Pathog. 2012;8(5):e1002697
references.pmid: 22589726
references.citation: PLoS One. 2011;6(10):e25582
references.pmid: 21991321
references.citation: Lancet. 2012 Mar 31;379(9822):1234-44
references.pmid: 22333947
references.citation: Immunology. 2006 Aug;118(4):429-37
references.pmid: 16895553
references.citation: Nat Rev Immunol. 2008 Jan;8(1):22-33
references.pmid: 18097447
references.citation: Ann Oncol. 1997 Oct;8(10):987-94
references.pmid: 9402172
references.citation: Int J Cancer. 2009 Apr 1;124(7):1721-6
references.pmid: 19089927
references.citation: Malar J. 2008 Nov 18;7:238
references.pmid: 19019204
references.citation: Trends Parasitol. 2007 Dec;23(12):596-604
references.pmid: 17980663
references.citation: Blood. 2005 Aug 1;106(3):1031-6
references.pmid: 15840698
references.citation: Nat Rev Microbiol. 2008 Dec;6(12):913-24
references.pmid: 19008891
references.citation: Nature. 1970 Dec 12;228(5276):1056-8
references.pmid: 4320657
references.citation: Proc Natl Acad Sci U S A. 1983 Feb;80(3):820-4
references.pmid: 6402776
references.citation: J Exp Med. 2008 Aug 4;205(8):1797-805
references.pmid: 18625747
references.citation: J Exp Med. 2007 Feb 19;204(2):259-65
references.pmid: 17242162
references.citation: Br J Haematol. 2012 Mar;156(6):744-56
references.pmid: 22260300
references.citation: Blood. 2003 May 1;101(9):3574-80
references.pmid: 12511417
references.citation: Cytometry A. 2011 Nov;79(11):894-6
references.pmid: 21796774
references.citation: Blood. 2010 Jun 17;115(24):4976-8
references.pmid: 20558622
references.citation: J Natl Cancer Inst. 1969 Jan;42(1):19-28
references.pmid: 4303830
references.citation: Clin Vaccine Immunol. 2006 Mar;13(3):376-9
references.pmid: 16522780