DISTINCTIVE EXPRESSION PATTERN OF THE BCL-6 PROTEIN IN NODULAR LYMPHOCYTE PREDOMINANCE HODGKINS-DISEASE

The BCL-6 gene encoding a nuclear-located Kruppel-type zinc finger pro tein is rearranged in about 30% diffuse large B-cell lymphomas and is expressed predominantly in normal germinal center B cells and related lymphomas. These findings suggest that BCL-6 may play a role in regula ting differentiation of normal germinal center B cells and that its de -regulated expression caused by rearrangements may contribute to lymph omagenesis. This prompted us to investigate the expression of the BCL- 6 protein in Hodgkin's disease (HD), focusing on the nodular lymphocyt e predominance subtype (NLPHD), which differs from classical HD by vir tue of the B-cell nature of the malignant cell population (so-called L &H cells) and its relationship with germinal centers. Forty-one HD sam ples (19 NLPHD, 12 nodular sclerosis, and 10 mixed cellularity) were i mmunostained with the monoclonal antibodies PG-B6 and PG-B6p that reac t with a fixative-sensitive and a formalin-resistant epitope on the am inoterminal region of the BCL-6 gene product, respectively. Strong nuc lear positivity for the BCL-6 protein was detected in tumor (L&H) cell s in all cases of NLPHD. In contrast, BCL-6 was expressed only in a sm all percentage of Hodgkin and Reed-Sternberg cells in about 30% of cla ssical HD cases. Notably, the nuclei of reactive CD3(+)/CD4(+) T cells nearby to and resetting around L&H cells in NLPHD were also strongly BCL-6(+), but lacked CD40 ligand (CD40L) expression. This staining pat tern clearly differed from that of classical HD, whose cellular backgr ound was made up of CD3(+)/CD4(+) T cells showing the BCL-6(-)/CD40L() phenotype. These results further support the concept that NLPHD is a n histogenetically distinct, B-cell-derived subtype of HD and suggest a role for BCL-6 in its development. (C) 1996 by The American Society of Hematology.