Plasmodium chabaudi infection induces AID expression in transitional and marginal zone B cells.

INTRODUCTION

Endemic Burkitt's lymphoma (eBL) is associated with Epstein-Barr virus and repeated malaria infections. A defining feature of eBL is the translocation of the c-myc oncogene to the control of the immunoglobulin promoter. Activation-induced cytidine deaminase (AID) has been shown to be critical for this translocation. Malaria infection induces AID in germinal center B cells, but whether malaria infection more broadly affects AID activation in extrafollicular B cells is unknown.

METHODS

We either stimulated purified B cells from AID-green fluorescence protein (GFP) reporter mice or infected AID-GFP mice with Plasmodium chabaudi, AID fluorescence was monitored in B cell subsets by flow cytometry.

RESULTS

In vitro analysis of B cells from these mice revealed that CpG (a Toll-like receptor 9 ligand) was a potent inducer of AID in both mature and immature B cell subsets. Infection of AID-GFP mice with Plasmodium chabaudi demonstrated that AID expression occurs in transitional and marginal zone B cells during acute malaria infection. Transitional B cells were also capable of differentiating into antibody secreting cells when stimulated in vitro with CpG when isolated from a P. chabaudi-infected mouse.

CONCLUSIONS

These data suggest that P. chabaudi is capable of inducing AID expression in B cell subsets that do not participate in the germinal center reaction, suggesting an alternative role for malaria in the etiology of eBL.