ISSN:
1569-8041
Keywords:
chromosomal translocations
;
immunophenotype
;
leukemias
;
lymphomas
;
monoclonal antibodies
;
oncogenes
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
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 thebcl-6 gene at the protein level, two monoclonal antibodies (PG-B6a andPG-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 ofbcl-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-6was 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 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 forbcl-6 was consistently detected in tumor (L & 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 reactiveCD3+/CD4+ T-cells near to and rosetting around l & 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 is 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.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1023/A:1008202904659
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