Expression of the recombination activating genes (RAG1 and RAG2) is not detectable in Epstein-Barr virus-associated human lymphomas

Abstract

The expression of the recombination activating genes (RAG1 and RAG2) is largely restricted to immature lymphoid cells. Previous studies have suggested that Epstein-Barr virus (EBV) infection may lead to a re-induction of RAG expression in mature B lymphocytes. To assess the significance of this mechanism for the pathogenesis of malignant lymphomas, we have examined the expression of RAG genes in 11 cases of EBV-associated endemic Burkitt's lymphoma (BL), 25 cases of Hodgkin's disease (HD, 17 EBV(+), 8 EBV(-)) and 10 cases of follicular non-Hodgkin's lymphoma (NHL). Using in situ hybridization, expression of the RAGs was detected in cortical thymocytes in normal thymus and in the tumor cells of 2 of 3 lymphoblastic NHL. By contrast, there was no detectable RAG expression in the BL, HD and follicular NHL cases. Our results indicate that re-induction of RAG expression does not occur in human lymphomas in vivo. Thus, it is unlikely to play a role in the development of translocations involving immunoglobulin gene loci which are characteristically found in BL and follicular NHL. Moreover, our study shows that in situ hybridization is a suitable method for the analysis of RAG expression in human tissue sections.