BCL-6 protein expression in normal and neoplastic lymphoid tissues

B. Falini, M. Fizzotti, S. Pileri, A. Liso, L. Pasqualucci, L. Flenghi

Research output: Contribution to journalArticle

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Abstract

The human bcl-6 gene, which is rearranged in about 30% of diffuse large B-cell lymphomas (DLCL-B), encodes for a Kruppel-type zinc finger protein of 706 amino acids. In order to investigate the expression of the bcl-6 gene at the protein level, two monoclonal antibodies (PG-B6a and PG-B6p) directed against the human bcl-6 protein were generated by immunizing Balb/c mice with a recombinant protein corresponding to the amino-terminal region (amino acids 3-484) of bcl-6. PG-B6a (a = avian) recognized the most conserved bcl-6 epitope (expressed in many animal species, including avian). PG-B6p (p = paraffin) reacted with an epitope of bcl-6 partially resistant to fixatives and detectable on microwave-heated paraffin sections. At immunocytochemistry, bcl-6 localized in the nucleus with a microgranular or diffuse pattern. Strong nuclear expression of bcl-6 was mainly detected in normal germinal- center B-cells, whereas mantle- and marginal-zone B cells, as well as plasma cells and marrow B-cell precursors, did not express bcl-6. These immunohistological findings strongly suggest that bcl-6 may play a role as a regulator of germinal-center related functions. All MoAbs stained neoplastic cells of follicular lymphomas, DLCL-B, and Burkitt's lymphomas. In DLCL-B, bcl-6 expression was independent of bcl-6 gene rearrangements and did not correlate with expression of other markers or the proliferation index. Among low-grade B-cell lymphomas, immunostaining for bcl-6 proved useful for differentiating proliferation centers in B-CLL (bcl-2+/bcl-6-) from trapped germinal centers in mantle-cell lymphomas (bcl-2-/bcl-6+). Strong nuclear positivity for bcl-6 was consistently detected in tumor (L and H) cells of nodular, lymphocyte-predominant Hodgkin's disease (NLPHD). These results further support the concept that NLPHD is a histogenetically distinct (germinal-center derived) subtype of HD. Notably, the nuclei of reactive CD3+/CD4+ T cells near to and rosetting around L and H cells in NLPHD were also strongly bcl-6+, but lacked CD40 ligand (CD40L) expression. This staining pattern clearly differed from that of classic HD, whose cellular background was made up of CD3+/CD4+ T cells showing the bcl-6-/CD40L+ phenotype. The above immunohistological findings suggest that (a) bcl-6 may play a role in regulating B-cell differentiation step(s) occurring within germinal centers; (b) deregulated bcl-6 expression caused by rearrangements may contribute to B-lymphomagenesis: (c) bcl-6 is possibly involved in the pathogenesis of NLPHD.

Original languageEnglish
JournalAnnals of Oncology
Volume8
Issue numberSUPPL. 2
Publication statusPublished - 1997

Fingerprint

Germinal Center
Lymphoid Tissue
Hodgkin Disease
B-Lymphocytes
Lymphocytes
CD40 Ligand
B-Cell Lymphoma
Proteins
Paraffin
Epitopes
T-Lymphocytes
Mantle-Cell Lymphoma
Amino Acids
Fixatives
Follicular Lymphoma
B-Lymphoid Precursor Cells
Burkitt Lymphoma
Gene Rearrangement
Zinc Fingers
Microwaves

Keywords

  • Chromosomal translocations
  • Immunophenotype
  • Leukemias
  • Lymphomas
  • Monoclonal antibodies
  • Oncogenes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Falini, B., Fizzotti, M., Pileri, S., Liso, A., Pasqualucci, L., & Flenghi, L. (1997). BCL-6 protein expression in normal and neoplastic lymphoid tissues. Annals of Oncology, 8(SUPPL. 2).

BCL-6 protein expression in normal and neoplastic lymphoid tissues. / Falini, B.; Fizzotti, M.; Pileri, S.; Liso, A.; Pasqualucci, L.; Flenghi, L.

In: Annals of Oncology, Vol. 8, No. SUPPL. 2, 1997.

Research output: Contribution to journalArticle

Falini, B, Fizzotti, M, Pileri, S, Liso, A, Pasqualucci, L & Flenghi, L 1997, 'BCL-6 protein expression in normal and neoplastic lymphoid tissues', Annals of Oncology, vol. 8, no. SUPPL. 2.
Falini B, Fizzotti M, Pileri S, Liso A, Pasqualucci L, Flenghi L. BCL-6 protein expression in normal and neoplastic lymphoid tissues. Annals of Oncology. 1997;8(SUPPL. 2).
Falini, B. ; Fizzotti, M. ; Pileri, S. ; Liso, A. ; Pasqualucci, L. ; Flenghi, L. / BCL-6 protein expression in normal and neoplastic lymphoid tissues. In: Annals of Oncology. 1997 ; Vol. 8, No. SUPPL. 2.
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T1 - BCL-6 protein expression in normal and neoplastic lymphoid tissues

AU - Falini, B.

AU - Fizzotti, M.

AU - Pileri, S.

AU - Liso, A.

AU - Pasqualucci, L.

AU - Flenghi, L.

PY - 1997

Y1 - 1997

N2 - The human bcl-6 gene, which is rearranged in about 30% of diffuse large B-cell lymphomas (DLCL-B), encodes for a Kruppel-type zinc finger protein of 706 amino acids. In order to investigate the expression of the bcl-6 gene at the protein level, two monoclonal antibodies (PG-B6a and PG-B6p) directed against the human bcl-6 protein were generated by immunizing Balb/c mice with a recombinant protein corresponding to the amino-terminal region (amino acids 3-484) of bcl-6. PG-B6a (a = avian) recognized the most conserved bcl-6 epitope (expressed in many animal species, including avian). PG-B6p (p = paraffin) reacted with an epitope of bcl-6 partially resistant to fixatives and detectable on microwave-heated paraffin sections. At immunocytochemistry, bcl-6 localized in the nucleus with a microgranular or diffuse pattern. Strong nuclear expression of bcl-6 was mainly detected in normal germinal- center B-cells, whereas mantle- and marginal-zone B cells, as well as plasma cells and marrow B-cell precursors, did not express bcl-6. These immunohistological findings strongly suggest that bcl-6 may play a role as a regulator of germinal-center related functions. All MoAbs stained neoplastic cells of follicular lymphomas, DLCL-B, and Burkitt's lymphomas. In DLCL-B, bcl-6 expression was independent of bcl-6 gene rearrangements and did not correlate with expression of other markers or the proliferation index. Among low-grade B-cell lymphomas, immunostaining for bcl-6 proved useful for differentiating proliferation centers in B-CLL (bcl-2+/bcl-6-) from trapped germinal centers in mantle-cell lymphomas (bcl-2-/bcl-6+). Strong nuclear positivity for bcl-6 was consistently detected in tumor (L and H) cells of nodular, lymphocyte-predominant Hodgkin's disease (NLPHD). These results further support the concept that NLPHD is a histogenetically distinct (germinal-center derived) subtype of HD. Notably, the nuclei of reactive CD3+/CD4+ T cells near to and rosetting around L and H cells in NLPHD were also strongly bcl-6+, but lacked CD40 ligand (CD40L) expression. This staining pattern clearly differed from that of classic HD, whose cellular background was made up of CD3+/CD4+ T cells showing the bcl-6-/CD40L+ phenotype. The above immunohistological findings suggest that (a) bcl-6 may play a role in regulating B-cell differentiation step(s) occurring within germinal centers; (b) deregulated bcl-6 expression caused by rearrangements may contribute to B-lymphomagenesis: (c) bcl-6 is possibly involved in the pathogenesis of NLPHD.

AB - The human bcl-6 gene, which is rearranged in about 30% of diffuse large B-cell lymphomas (DLCL-B), encodes for a Kruppel-type zinc finger protein of 706 amino acids. In order to investigate the expression of the bcl-6 gene at the protein level, two monoclonal antibodies (PG-B6a and PG-B6p) directed against the human bcl-6 protein were generated by immunizing Balb/c mice with a recombinant protein corresponding to the amino-terminal region (amino acids 3-484) of bcl-6. PG-B6a (a = avian) recognized the most conserved bcl-6 epitope (expressed in many animal species, including avian). PG-B6p (p = paraffin) reacted with an epitope of bcl-6 partially resistant to fixatives and detectable on microwave-heated paraffin sections. At immunocytochemistry, bcl-6 localized in the nucleus with a microgranular or diffuse pattern. Strong nuclear expression of bcl-6 was mainly detected in normal germinal- center B-cells, whereas mantle- and marginal-zone B cells, as well as plasma cells and marrow B-cell precursors, did not express bcl-6. These immunohistological findings strongly suggest that bcl-6 may play a role as a regulator of germinal-center related functions. All MoAbs stained neoplastic cells of follicular lymphomas, DLCL-B, and Burkitt's lymphomas. In DLCL-B, bcl-6 expression was independent of bcl-6 gene rearrangements and did not correlate with expression of other markers or the proliferation index. Among low-grade B-cell lymphomas, immunostaining for bcl-6 proved useful for differentiating proliferation centers in B-CLL (bcl-2+/bcl-6-) from trapped germinal centers in mantle-cell lymphomas (bcl-2-/bcl-6+). Strong nuclear positivity for bcl-6 was consistently detected in tumor (L and H) cells of nodular, lymphocyte-predominant Hodgkin's disease (NLPHD). These results further support the concept that NLPHD is a histogenetically distinct (germinal-center derived) subtype of HD. Notably, the nuclei of reactive CD3+/CD4+ T cells near to and rosetting around L and H cells in NLPHD were also strongly bcl-6+, but lacked CD40 ligand (CD40L) expression. This staining pattern clearly differed from that of classic HD, whose cellular background was made up of CD3+/CD4+ T cells showing the bcl-6-/CD40L+ phenotype. The above immunohistological findings suggest that (a) bcl-6 may play a role in regulating B-cell differentiation step(s) occurring within germinal centers; (b) deregulated bcl-6 expression caused by rearrangements may contribute to B-lymphomagenesis: (c) bcl-6 is possibly involved in the pathogenesis of NLPHD.

KW - Chromosomal translocations

KW - Immunophenotype

KW - Leukemias

KW - Lymphomas

KW - Monoclonal antibodies

KW - Oncogenes

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