Introduction

• a 96 kDa nuclear protein selectively expressed in mature B cells within normal germinal centers as well as in their transformed counterparts in diffuse large B cell lymphoma. PMID: 12879322

• a transcriptional repressor that prevents the terminal differentiation of mature B-cells to plasma cells, and is essential for germinal center formation in the primary lymphoid organs of mammals. PMID: 16076494

• a zinc finger transcription factor that is highly expressed in normal germinal center B-cells. PMID: 15998973

• an important regulator of the immune system. PMID: 12469325

• encodes a zinc finger transcription factor which is selectively expressed by germinal center (GC) B-cells, but not by pre-GC or post-GC B-cells. PMID: 9720713

• a POZ/zinc-finger protein, is a sequence-specific transcriptional repressor. PMID: 8692924

• a transcriptional repressor required for germinal center formation. PMID: 16147992

Normal Expression

• normally expressed in germinal center B cells where it is believed to have a developmental or differentiation function. PMID: 9389359

• expressed in mammary epithelium in nonpregnant animals as well as during early pregnancy. PMID: 12944904

• the bcl-6 protein has also been reported to be expressed in normal skin and epidermal neoplasms. PMID: 12879322

• expressed by most cortical thymocytes and by scattered medullary thymocytes. PMID: 11133771

• In lymph nodes, expression of Bcl-6 protein is restricted to germinal center (GC) B-cells and 10% to 15% of CD3/CD4+ intrafollicular T cells. PMID: 10208461

• With the use of immunohistochemistry, bcl-6 protein was shown to stain intensely on normal prickle cells, but none to only slightly on epidermal basal cells. PMID: 9311010

• expressed at high levels in germinal center B-cells as a 92-98 kDa nuclear protein in a constitutively phosphorylated form. PMID: 9188861

• 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. PMID: 9209651

• BCL-6 protein expression was threefold to 34-fold higher in germinal center B cells than in resting B cells. PMID: 8652841

• BCL-6 protein is consistently expressed in reactive lymphoid tissues, where it is restricted to the follicle centre. The protein is also widely expressed in non-Hodgkin's lymphomas (NHL). PMID: 8758205

• BCL-6 protein was localized in the nuclei of most of the germinal center B cells and a small number of marginal zone B cells. Furthermore, BCL-6 protein was expressed in follicular, Burkitt's, and diffuse large B-cell lymphomas. PMID: 7795234

• The Bcl6 gene encodes a sequence-specific transcriptional repressor and is ubiquitously expressed in adult murine tissues including heart muscle. PMID: 10533607

• In selected tissues from postnatal mouse, bcl6 expression was detected in brain, renal cortex, spleen, and thymus. PMID: 9642131

Abnormal Expression

• expressed in germinal centre derived B-cell non-Hodgkin lymphomas including diffuse large B-cell lymphoma (DLBCL). PMID: 17701581

• Bcl-6 expression is common in Grade 1 Follicle center cell lymphoma (FCCL) (100%) and rare in other indolent B-cell lymphomas(BCL). PMID: 11378576

• It was shown that the neoplastic cells in 71% of diffuse large B-cell lymphoma (DLBCLs) and 100% of follicular lymphoma (FLs) expressed bcl-6 protein. Expression of bcl-6 was seen more frequently in diffuse large B-cell lymphomas with large noncleaved morphology compared with immunoblastic morphology (82% v 27%, P = .0015), but failed to correlate with 3q27 abnormalities. PMID: 10414499

• bcl-6 protein only in the high-grade components in four of eight high-grade MALT lymphoma cases and in four of six gastric DLL cases. PMID: 9504689

• Strong nuclear positivity for the BCL-6 protein was detected in tumor (L&H) cells in all cases of nodular lymphocyte predominance subtype (NLPHD). In contrast, BCL-6 was expressed only in a small percentage of Hodgkin and Reed-Sternberg cells in about 30% of classical Hodgkin's disease (HD) cases. PMID: 8555467

Diagnostic & Therapeutic Value

• In this group of 33 patients with primary central nervous system lymphoma (PCNSL), expression of BCL-6 was significantly associated with longer overall survival. PMID: 12631608

Applications

Immunocytochemistry (ICC)

• By immunocytochemical analysis, BCL-6 localizes in the nucleus where PG-B6 staining gives a microgranular/diffuse pattern with exclusion of the nucleoli. The main reactivity of PG-B6 in tonsil and spleen is with the nuclei of germinal center B cells, whereas B cells within the mantle and marginal zones do not express BCL-6. PMID: 7639334

Immunohistochemistry (IHC)

• Immunostaining for Bcl-6 and CD10 was done using formalin-fixed, paraffin-embedded sections and was examined independently by three pathologists. PMID: 12766583

• In this study the authors explored the value of immunostaining for follicular center B-cell markers, BCL-6 and CD10, in paraffin sections as a tool for the differential diagnosis of B-cell lymphomas. PMID: 10843287

• were evaluated for BCL-6 protein expression by immunohistochemistry on frozen sections and cell smears. PMID: 9310496

Western Blotting (WB)

• Bcl-6 was also detected in 5 of 5 FCL and 1 of 3 MZL but in no SLL or MCL by Western blot analysis in 14 cases with lymphoid disorders. PMID: 10396291

• 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. PMID: 7795255