BCL-6 PROTEIN IS EXPRESSED IN GERMINAL-CENTER B-CELLS

Structural alterations of the 5' noncoding region of the BCL-6 gene ha ve been found in 40% of diffuse large cell lymphoma (DLCL) and 5% to 1 0% of follicular lymphomas (FL), suggesting that deregulated BCL-6 exp ression may play a role in lymphomagenesis. Nucleotide sequencing of B CL-6 cDNA predicted a protein containing six zinc-finger domains, sugg esting that it may function as a transcription factor. Using antisera raised against N- and C-terminal BCL-6 synthetic oligopeptides in immu noprecipitation, immunoblot, and immunocytochemical assays, this study identifies the BCL-6 gene product as a 95-kD nuclear protein, Western blot analysis of human tumor cell lines representative of various hem atopoietic lineages/stages of differentiation showed that the BCL-6 pr otein is predominantly expressed in the B-cell lineage where it was fo und in mature B cells, Immunohistochemical analysis of normal human ly mphoid tissues indicated that BCL-6 expression is topographically rest ricted to germinal centers including all centroblasts and centrocytes. The BCL-6 protein was also detectable in inter- and intrafollicular C D4(+) T cells, but not in other follicular components including mantle -zone B cells, plasma cells, dendritic cells, and macrophages. Immunoh istochemical analysis of DLCL and FL biopsy samples showed that the BC L-6 protein is detectable in these tumors independent of the presence of BCL-6 gene rearrangements. These results indicate that the expressi on of the BCL-6 gene is specifically regulated during B-cell different iation and suggest a role for BCL-6 in germinal center development or function. Because DLCL derive from germinal-center B cells, deregulate d BCL-6 expression may contribute to lymphomagenesis by preventing pos tgerminal center differentiation. (C) 1995 by The American Society of Hematology.