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AIDS Primary Central Nervous System Lymphoma: Molecular Analysis of the Expressed V_H Genes and Possible Implications for Lymphomagenesis¹

Sylvie Julien^*, Mirjana Radosavljevic^*, Nathalie Labouret^*, Sophie Camilleri-Broet, Frederic Davi, Martine Raphael, Thierry Martin^* and Jean-Louis Pasquali^2,*

^* Laboratoire d’Immunopathologie, Centre de Recherche d’Immunohématologie, Hôpital Civil, Hôpitaux Universitaires, Strasbourg, France; and Service d’Hematologie Biologique, Hôpital Avicenne, Bobigny, France

AIDS-associated primary central nervous system lymphomas are late events that have an extremely poor prognosis. Despite different hypotheses, the brain localization of these B cell lymphomas remains an enigma. To better define the cell origin of the lymphomas and the possible role of the B cell receptor (BCR) in the brain localization and/or in the oncogenic transformation, we analyzed the V region genes of the Ig heavy chain expressed by lymphoma cells in five randomly selected patients. After amplifying the rearranged V_HDJ_H DNA by PCR, cloning, and sequencing of the amplified products, we observed that: 1) of the five lymphomas analyzed, four were clearly monoclonal; 2) there was no preferential use of one peculiar V_H family or one peculiar 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 was no intraclonal variability, suggesting that the hypermutation mechanism is no longer efficient in these lymphoma B cells. Taken together, 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 responsible for the brain localization of these B cells bearing mutated BCR, other factors must be involved in B cell transformations in primary central nervous system lymphoma.

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