BURKITTS LYMPHOMAS EXPRESS V-H GENES WITH A MODERATE NUMBER OF ANTIGEN-SELECTED SOMATIC MUTATIONS

The normal counterpart of the neoplastic B cells occurring in Burkitt' s lymphomas (BL) is an issue of controversial debate. To clarify this matter, a semi-nested Primer polymerase chain reaction was performed t o amplify the VDJ rearrangements of the immunoglobulin heavy chain (V- H) gene of DNA extracts from 10 (8 sporadic and 2 endemic) BL; cases. The resulting amplificates were sequenced for comparison with known ge rm line V-H segments. The control cases comprised six cases of B cell chronic lymphocytic leukemia and six cases of mantle cell lymphoma kno wn to display native nonmutated ie, pre-germinal center V-H configurat ions; and eight cases of follicular center lymphoma known to display m utated V-H genes with signs of a still-ongoing mutation reaction, char acteristic for germinal center cells and lymphomas that derive therefr om. The results of this approach revealed that both sporadic and endem ic BL; express mutated V-H genes with a mutation frequency considerabl y lower (4.9% and 5.4%, respectively) than that observed in follicular center lymphoma (11.8%) in addition, after subcloning the amplificate s, sequence analysis revealed no signs of ongoing mutations These resu lts led us to conclude that the derivation of neoplastic B cells in BL is definitely not from naive, nonmutated pre-germinal center B cells, Instead, our findings support the view that BI; cells stem either fro m early centroblasts that are arrested after an initial hypermutation reaction, or from germinal center B cells that have differentiated in terms of surface immunoglobulin profile and mutation Pattern but not i n terms of morphology and proliferation toward SIgM(+) IgD(-) memory B cells because of the deregulated c-myc gene expression.