TCL1 oncogene expression in B cell subsets from lymphoid hyperplasia and distinct classes of B cell lymphoma

Activation of the TCL1 oncogene has been implicated in T cell leukemias/lym phomas and recently was associated with AIDS diffuse large B cell lymphomas (AIDS-DLBCL). Also, in nonmalignant lymphoid tissues, antibody staining ha s shown that mantle zone B cells expressed abundant Tcl1 protein, whereas g erminal center (GC; centrocytes and centroblasts) B cells showed markedly r educed expression. Here, we analyze isolated B cell subsets from hyperplast ic tonsil to determine a more precise pattern of Tcl1 expression with devel opment. We also examine multiple B cell lines and B lymphoma patient sample s to determine whether different tumor classes retain or alter the developm ental pattern of expression. We show that TCL1 expression is not affected b y Epstein-Barr virus (EBV) infection and is high in naive B cells, reduced in GC B cells, and absent in memory B cells and plasma cells. Human herpesv irus-8 infected primary effusion lymphomas (PEL) and multiple myelomas are uniformly TCL1 negative, whereas all other transformed B cell lines tested express moderate to abundant TCL1. This observation supports the hypothesis that PEL, like myeloma, usually arise from post-GC stages of B cell develo pment. Tell protein is also detected in most naive/GC-derived B lymphoma pa tient samples (23 of 27 [85%] positive), whereas most post-GC-derived B lym phomas lack expression (10 of 41 [24%] positive). These data indicate that the pattern of Tell expression is distinct between naive/GC and post-GC-der ived B lymphomas (P < 0.001) and that the developmental pattern of expressi on is largely retained. However, post-GC-derived AIDS-DLBCL express TCL1 at a frequency equivalent to naive/GC-derived B lymphomas in immune-competent individuals (7 of 9 [78%] positive), suggesting that TCL1 down-regulation is adversely affected by severe immune system dysfunction. These findings d emonstrate that TCL1 expression in B cell lymphoma usually reflects the sta ge of B cell development from which they derive, except in AIDS-related lym phomas.