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BCL-6 protein is expressed in germinal-center B cells
G Cattoretti, CC Chang, K Cechova, J Zhang, BH Ye, B Falini, DC Louie, K Offit, RS Chaganti and R Dalla-Favera
Department of Pathology, College of Physicians & Surgeons, Columbia
University, New York, NY 10032, USA.
Structural alterations of the 5' noncoding region of the BCL-6 gene have
been found in 40% of diffuse large cell lymphoma (DLCL) and 5% to 10% of
follicular lymphomas (FL), suggesting that deregulated BCL-6 expression may
play a role in lymphomagenesis. Nucleotide sequencing of BCL-6 cDNA
predicted a protein containing six zinc-finger domains, suggesting that it
may function as a transcription factor. Using antisera raised against N-
and C-terminal BCL-6 synthetic oligopeptides in immunoprecipitation,
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 hematopoietic lineages/stages of
differentiation showed that the BCL-6 protein is predominantly expressed in
the B-cell lineage where it was found in mature B cells.
Immunohistochemical analysis of normal human lymphoid tissues indicated
that BCL-6 expression is topographically restricted to germinal centers
including all centroblasts and centrocytes. The BCL-6 protein was also
detectable in inter- and intra-follicular CD4+ T cells, but not in other
follicular components including mantle-zone B cells, plasma cells,
dendritic cells, and macrophages. Immunohistochemical analysis of DLCL and
FL biopsy samples showed that the BCL-6 protein is detectable in these
tumors independent of the presence of BCL-6 gene rearrangements. These
results indicate that the expression of the BCL-6 gene is specifically
regulated during B-cell differentiation and suggest a role for BCL-6 in
germinal center development or function. Because DLCL derive from
germinal-center B cells, deregulated BCL-6 expression may contribute to
lymphomagenesis by preventing postgerminal center differentiation.
Volume 86,
Issue 1,
pp. 45-53,
07/01/1995
Copyright © 1995 by The American Society of Hematology
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