A B cell riddle: a new tool to study the link between malaria and Burkitt’s Lymphoma (TUM5P.935)

Burkitt’s lymphomas (BLs) are B cell lineage tumors that are the most common childhood cancer in the P. falciparum malaria endemic areas of Africa. The molecular basis of malaria infection causing endemic BLs (eBLs) remains unknown. Recent data has confirmed that remarkably 30% of eBLs are enriched for one particular heavy chain V region, VH4-34. The US frequency in normal individuals is 4%, however it was unknown in endemic regions of Africa. This high frequency of VH4-34 in eBLs initiated the use of the anti-VH4-34 antibody, ‘9G4’, to study VH4-34 at the cellular level in Africa. Here we report that in adults and children living in a malaria endemic area of Mali, VH4-34 expressing B cells are present in frequencies similar to those in individuals in the U.S, however more B cells are found in memory B cell subpopulations. We have also found that VH4.34 circulating antibody levels increase when infected with malaria but do not significantly increase with age unlike other malaria specific antibodies. This suggests the VH4-34 heavy chain is possibly important for malaria, but is decreased from the repertoire after infection is controlled. We are initiating studies to determine: the frequency of VH4-34 expressing B cells latently infected with EBV to see if it enriched, whether VH4-34 Abs are protective in malaria, and elucidating a molecular mechanism for transformation. This data will start an avenue to better understand the complex mechanisms behind this childhood cancer.