TY - JOUR
T1 - BCL-6 protein is expressed in germinal-center B cells
AU - Cattoretti, Giorgio
AU - Chang, Chih Chao
AU - Cechova, Katarina
AU - Zhang, Jiandong
AU - Ye, Bihui H.
AU - Falini, Brunangelo
AU - Louie, Diane C.
AU - Offit, Kenneth
AU - Chaganti, R. S.K.
AU - Dalla-Favera, Riccardo
N1 - Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 1995/7/1
Y1 - 1995/7/1
N2 - 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 intrafollicular 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.
AB - 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 intrafollicular 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.
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U2 - 10.1182/blood.v86.1.45.bloodjournal86145
DO - 10.1182/blood.v86.1.45.bloodjournal86145
M3 - Article
C2 - 7795255
AN - SCOPUS:0029045421
SN - 0006-4971
VL - 86
SP - 45
EP - 53
JO - Blood
JF - Blood
IS - 1
ER -