AIDS primary central nervous system lymphoma: Molecular analysis of the expressed V-H genes and possible implications for lymphomagenesis

AIDS-associated primary central nervous system lymphomas are late events th at have an extremely poor prognosis. Despite different hypotheses, the brai n localization of these B cell lymphomas remains an enigma, To better defin e the cell origin of the lymphomas and the possible role of the B cell rece ptor (BCR) in the brain localization and/or in the oncogenic transformation , we analyzed the V region genes of the Ig heavy chain expressed by lymphom a cells in five randomly selected patients. After amplifying the rearranged V(H)DJ(H) DNA by PCR, cloning, and sequencing of the amplified products, w e observed that: 1) of the five lymphomas analyzed, four were clearly monoc lonal; 2) there was no preferential use of one peculiar V-H family or one p eculiar segment of gene; 3) the mutation analysis showed that an Ag-driven process occurred in at least two cases, probably before the oncogenic event ; and 4) there,vas no intraclonal variability, suggesting that the hypermut ation mechanism is no longer efficient in these lymphoma B cells. Taken tog ether, our results suggest that distinct Ags could be recognized by the BCR of the lymphoma cells in different patients and that, if the Ags are respo nsible for the brain localization of these B cells bearing mutated BCR, oth er factors must be involved in B cell transformations in primary central ne rvous system lymphoma.