BCL6 (Ab-333) Antibody

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Product Specs

Form
Rabbit IgG in phosphate buffered saline (without Mg2+ and Ca2+), pH 7.4, 150mM NaCl, 0.02% sodium azide and 50% glycerol.
Lead Time
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Synonyms
B cell CLL/lymphoma 6 antibody; B cell lymphoma 6 protein antibody; B-cell lymphoma 5 protein antibody; B-cell lymphoma 6 protein antibody; BCL 5 antibody; Bcl 6 antibody; BCL-5 antibody; BCL-6 antibody; BCL5 antibody; BCL6 antibody; BCL6_HUMAN antibody; BCL6A antibody; cys his2 zinc finger transcription factor antibody; cys-his2 zinc finger transcription factor antibody; LAZ 3 antibody; LAZ 3 protein antibody; LAZ3 antibody; Lymphoma Associated Zinc Finger Gene On Chromosome 3 (LAZ3) antibody; Lymphoma associated zinc finger gene on chromosome 3 antibody; Protein LAZ-3 antibody; ZBTB 27 antibody; ZBTB27 antibody; Zinc finger and BTB domain containing protein 27 antibody; Zinc finger and BTB domain-containing protein 27 (ZBTB27) antibody; Zinc finger and BTB domain-containing protein 27 antibody; Zinc Finger Protein 51 (ZNF51) antibody; Zinc finger protein 51 antibody; zinc finger transcription factor BCL6S antibody; ZNF 51 antibody; ZNF51 antibody
Target Names
Uniprot No.

Target Background

Function
BCL6 is a transcriptional repressor essential for germinal center (GC) formation and antibody affinity maturation. Its mechanisms of action are lineage-specific and influence various biological functions. BCL6 forms complexes with different corepressors and histone deacetylases, repressing the transcriptional expression of target genes. It can repress target genes by directly binding to the DNA sequence 5'-TTCCTAGAA-3' (BCL6-binding site) or indirectly by repressing the transcriptional activity of other transcription factors. In GC B-cells, BCL6 represses genes involved in differentiation, inflammation, apoptosis, and cell cycle control. It also autoregulates its own transcriptional expression and indirectly upregulates the expression of genes critical for GC reactions, such as AICDA, through the repression of microRNA expression, like miR155. BCL6's crucial role is to enable GC B-cells to proliferate rapidly in response to T-cell-dependent antigens while tolerating the physiological DNA breaks needed for immunoglobulin class switch recombination and somatic hypermutation without triggering p53/TP53-dependent apoptosis. In follicular helper CD4(+) T-cells (T(FH) cells), BCL6 promotes the expression of T(FH)-related genes while inhibiting the differentiation of T(H)1, T(H)2, and T(H)17 cells. It is also required for establishing and maintaining immunological memory for both T- and B-cells. BCL6 suppresses macrophage proliferation by competing with STAT5 for STAT-binding motifs on target genes, such as CCL2 and CCND2. In response to genotoxic stress, BCL6 controls cell cycle arrest in GC B-cells through both p53/TP53-dependent and -independent mechanisms. Additionally, BCL6 regulates neurogenesis by altering the composition of NOTCH-dependent transcriptional complexes at specific NOTCH targets, such as HES5, including the recruitment of the deacetylase SIRT1. This results in epigenetic silencing and neuronal differentiation.
Gene References Into Functions
  1. Our exploratory study indicates that EOMES, BCL6, and GZMB gene expression are abnormal within the PB T cell transcriptome of HT patients. We suggest a potential association of this transcription signature with HT heterogeneity and disease control. PMID: 29319368
  2. Cryptic t(3;8)(q27;q24) and/or MYC-BCL6 linkage associated with MYC expression by immunohistochemistry is frequent in multiple-hit B-cell lymphomas. PMID: 28665415
  3. BCL6 overexpression in SHR reduced blood pressure, NLRP3 expression, and inflammation in the renal cortex of SHR. PMID: 29072703
  4. While BCL6 regulates follicular helper T cells activity in both humans and mice, miR-31's role is restricted to human follicular helper T cell differentiation, suggesting species specificity of miR-31's action. PMID: 29133396
  5. Aberrant CD10 and BCL6 expression defines a subset of MCLs with a higher mean Ki-67 index and a higher prevalence of MUM1 expression. PMID: 28628241
  6. BCL6 acts as a growth-promoting factor in glioblastoma and glioma. PMID: 28356518
  7. IFN gamma induced upregulation of BCL6 was dependent on the classical STAT1 signaling pathway and affected both major BCL6 variants. Notably, although IFN alpha induced stronger STAT1 phosphorylation than IFN gamma, it only slightly upregulated BCL6 in multiple myeloma lines. PMID: 29510136
  8. Our findings show that miR-519d downregulates BCL6 expression by targeting its 3'-UTR. Moreover, BCL6 mediates the repression of miR-519d on cell proliferation and invasive capability of gastric cancer cells. PMID: 29510377
  9. In the Pakistani population, the frequency of GCB type DLBCL [diffuse large B cell lymphoma] expressing CD10 and BCL6 is 37.5%, while non-GCB type DLBCL [diffuse large B cell lymphoma] expressing MUM1 is 62.5%. PMID: 29056123
  10. BCOR internal tandem duplication and/or nuclear immunoreactivity for BCOR or BCL6 can assist in the diagnosis of primitive myxoid mesenchymal tumor of infancy and help differentiate it from congenital infantile fibrosarcoma. PMID: 28256570
  11. Our findings provide a novel apoptotic regulatory pathway where LITAF, as a transcription factor, inhibits the expression of BCL6, leading to activation of the intrinsic mitochondrial pathway and tumor apoptosis. PMID: 27764808
  12. Ikaros regulates the expression of the BCL6/BACH2 axis in acute lymphoblastic leukemia cells. PMID: 28030830
  13. Our research sheds new light on the biology of mantle cell lymphoma (MCL), revealing the role of SOX11 exerting a functional effect through the repression of BCL6 transcription in MCL cells. PMID: 26710884
  14. BCL6 inhibitors have demonstrated potent effects against these tumor types. Furthermore, mechanism-based combinations of BCL6 inhibitors with other agents have yielded synergistic and often dramatic activity. Hence, there is a compelling case to accelerate the development of BCL6-targeted therapies for translation to the clinical setting. PMID: 27881582
  15. High BCL6 expression is associated with a good response to chemotherapy in acute lymphoblastic leukemia. PMID: 27015556
  16. BCL6 expression is present in isolated cortical neurons, granule cells in the cerebellum, scattered glial cells, and in some cells of the ependyma and choroid plexus. PMID: 26862951
  17. We demonstrate that human follicular lymphomas are dependent on BCL6. PMID: 28232365
  18. Aberrant BCL6 expression was strongly associated with poor reproductive outcomes in IVF cycles in women with unexplained infertility. PMID: 29126613
  19. EBNA3C inhibits the transcriptional activity of the Bcl6 promoter through interaction with the cellular protein IRF4. PMID: 28738086
  20. Data suggest that B-cell CLL/lymphoma 6 is a promising candidate as a single diagnostic biomarker for detecting endometriosis in women with otherwise unexplained infertility and may be associated with endometrial dysfunction, including progesterone resistance. PMID: 27222232
  21. The objective of this study was to investigate the clinical significance of three immune cell-related transcription factors, T-bet, GATA-3, and Bcl-6, in bladder cancer in Tunisian patients. PMID: 27237631
  22. Analysis of BCL6's role in maintaining activated B cell diffuse large B cell lymphoma reveals that ABC-DLBCL is a BCL6-dependent disease that can be targeted by rationally designed inhibitors that exceed the binding affinity of natural BCL6 ligands. PMID: 27482887
  23. Results provide evidence that BCL6 overexpression is involved in genomic instability in multiple myeloma cells. PMID: 28544233
  24. Our data reveal a regulatory role of BCL6 in inhibiting antiviral resistance factors in follicular Th cells. PMID: 28550121
  25. High expressions of BCL6 and Lewis y antigen are associated with the development, high tumor burden, and worse prognosis of ovarian cancer. Targeting BCL6 could represent a novel therapeutic strategy for ovarian cancer treatment. PMID: 28671040
  26. In both mouse and human B cells, IFN-gamma synergized with B cell receptor, toll-like receptor, and/or CD40 activation signals to promote cell-intrinsic expression of the GC master transcription factor, B cell lymphoma 6 protein. PMID: 27069113
  27. MicroRNA-544 down-regulates both Bcl6 and Stat3 to inhibit tumor growth of human triple negative breast cancer. PMID: 27186677
  28. miR-10a directly recognizes the 3'-UTR of the BCL6 transcript and regulates BCL6 expression. PMID: 27815824
  29. This work identified BCL6 as a novel biomarker for early prediction of cerebral palsy. PMID: 28315684
  30. Bcl-6 expression in circulating follicular helper-like T cells may represent a reliable marker for disease activity in systemic lupus erythematosus. PMID: 27818202
  31. Subsequent single-crystal X-ray diffraction analysis of F1324/BCL6(5-129) complex revealed that F1324's high affinity was due to effective interaction of its side chains, while its main chain structure remained similar to that of BcoR(Arg498-514Pro). To our knowledge, F1324 is the strongest BCL6-binding peptide reported. PMID: 27856253
  32. We report the case of a 7-month-old girl with atypical oculo-facio-cardio-dental syndrome (OFCD). A novel de novo pathogenic mutation in the BCL6 interacting co-repressor gene (BCOR) (c.4540C>T; p.Arg1514*), was identified on the X chromosome. PMID: 28317252
  33. JAK2 is a direct BCL6 target gene; BCL6 bound to the JAK2 promoter. PMID: 27268052
  34. Deregulated BCL6 expression caused by hypermethylation and TET2 mutations may result in skewed follicular helper T cell differentiation and eventually contribute to angioimmunoblastic T-cell lymphoma and peripheral T-cell lymphoma development in patients. PMID: 27921272
  35. Data show a positive correlation between B cell lymphoma 6 (Bcl-6) and B lymphocyte-induced maturation protein 1 (Blimp-1) at the mRNA level. PMID: 27363279
  36. miR-155 overexpression plays a promoting role in the proliferative, migratory, and invasive behavior of OSCC cells. Its effects on OSCC are possibly associated with its regulation of the BCL6/cyclin D2 axis. PMID: 26986233
  37. BCL6 Rearrangements are associated with Diffuse Large B-Cell Lymphoma. PMID: 26319027
  38. Bcl6, by interacting with the co-factors NcoR2 and HDAC3, plays a pivotal role in controlling IRF7 induction and antiviral signaling priming. PMID: 26728228
  39. Diffuse large B-cell lymphoma patients with either MYC/BCL6 rearrangements or MYC/BCL6 co-expression did not always have a poorer prognosis. PMID: 26573234
  40. BCL6 promotes proliferation and survival of trophoblastic cells. PMID: 27029530
  41. Studies indicate that germinal centers (GC) B cells represent the normal counterpart of most B-cell lymphomas, which are often characterized by deregulated B cell lymphoma 6 (BCL6) expression or BCL6-mediated pathways. PMID: 26566802
  42. Bcl-6 mRNA and protein levels, as well as the frequencies of Bcl-6(+)CD4(+) cells were significantly increased in polyp tissues compared with normal controls. PMID: 25711734
  43. Follicular helper T cells differentiation is a multistage process involving BCL6 and other transcription factors, cytokines, and costimulation through ICOS and several other molecules. (Review) PMID: 26120879
  44. These results suggest that STAT6 plays an important role in regulating Sp1 and BCL6 through STAT2 to exert the anti-proliferative effects of type I IFN. PMID: 26945968
  45. Identified BCL6 to be a target of miR-10a in patients with Acute Myeloid Leukemia (AML). PMID: 26590574
  46. Study demonstrates that survivin belongs to the Tfh cell phenotype and ensures their optimal function by regulating transcriptional activity of Bcl-6. PMID: 26343374
  47. BCL6 repression of EP300 in human diffuse large B cell lymphoma cells provides a basis for rational combinatorial therapy. PMID: 21041953
  48. Taken together, our results demonstrated that miR-187-3p played a pivotal role in NSCLC through inhibiting cell proliferation, migration, invasion, and promoting apoptosis by targeting oncogenic BCL6. PMID: 26845350
  49. BCL6 gene expression plays a role in the pathogenesis of diffuse large B-cell lymphoma. PMID: 26414904

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Database Links

HGNC: 1001

OMIM: 109565

KEGG: hsa:604

STRING: 9606.ENSP00000232014

UniGene: Hs.478588

Involvement In Disease
Chromosomal aberrations involving BCL6 are a cause of B-cell non-Hodgkin lymphomas (B-cell NHL), including diffuse large B-cell lymphoma and follicular lymphoma. Approximately 40% of diffuse large B-cell lymphomas and 5 to 10% of follicular lymphomas are associated with chromosomal translocations that deregulate expression of BCL6 by juxtaposing heterologous promoters to the BCL6 coding domain. Translocation t(3;14)(q27;q32). Translocation t(3;22)(q27;q11) with immunoglobulin gene regions. Translocation t(3;7)(q27;p12) with IKZF1 gene 5'non-coding region. Translocation t(3;6)(q27;p21) with Histone H4. Translocation t(3;16)(q27;p11) with IL21R. Translocation t(3;13)(q27;q14) with LCP1.; DISEASE: Note=A chromosomal aberration involving BCL6 may be a cause of a form of B-cell leukemia. Translocation t(3;11)(q27;q23) with POU2AF1/OBF1.; DISEASE: Note=A chromosomal aberration involving BCL6 may be a cause of lymphoma. Translocation t(3;4)(q27;p11) with ARHH/TTF.
Subcellular Location
Nucleus.
Tissue Specificity
Expressed in germinal center T- and B-cells and in primary immature dendritic cells.

Q&A

BCL6 (Ab-333) Antibody: Research-Focused FAQs
Targeted for academic investigators studying BCL6 phosphorylation dynamics and functional regulation

What experimental controls are critical for studying BCL6 degradation via Ser333 phosphorylation?

Advanced controls for mechanistic studies:

  • Proteasome inhibition: Treat cells with MG-132 to confirm ubiquitin-proteasome-dependent degradation. BCL6 levels should stabilize despite phosphorylation .

  • Kinase modulation: Co-express constitutively active MEK (MEK-2E) or inhibit ERK1/2 to manipulate phosphorylation status. Monitor BCL6 mobility shifts via Phos-tag™ gels .

  • Time-course analysis: Collect samples at 0, 15, 30, and 60 min post anti-IgM stimulation in Ramos cells to correlate ERK2 activation with BCL6 degradation .

How can I resolve contradictions in BCL6 stability data across different B-cell models?

Troubleshooting framework:

  • Cell type variability: Compare germinal center (GC)-derived cells (e.g., Ramos) versus non-GC models (e.g., HEK293). BCL6 degradation is pronounced in GC-like contexts due to endogenous MAPK activity .

  • PEST motif integrity: Verify the presence of intact PEST domains (amino-terminal) in your BCL6 construct, as these are required for proteasomal targeting post-phosphorylation .

  • Cross-species reactivity: Confirm antibody compatibility with model organisms. BCL6 (Ab-333) shows reactivity in human and mouse but may fail in non-mammalian systems .

What integrated approaches link BCL6 phosphorylation to transcriptional repression activity?

Multi-omics strategy:

  • ChIP-seq: Map BCL6-DNA binding sites in phosphorylated (Ser333) vs. non-phosphorylated states using Ramos cells ± anti-IgM treatment .

  • RNA-seq: Identify differentially expressed genes (e.g., PDCD2, CDKN1A) upon BCL6 knockdown or MEK inhibition .

  • Proteomic profiling: Use SILAC labeling to quantify BCL6-interacting proteins (e.g., SMRT, HDAC3) under phosphorylation-mimetic conditions .

Example findings:

Phosphorylation StatusTranscriptional TargetsFunctional OutcomeCitation
Ser333-phosphorylatedPDCD2 upregulationPro-apoptotic shift
Non-phosphorylatedBCL2 repressionPro-survival

How do I design a study to explore BCL6’s dual roles in DNA repair and immune evasion?

Advanced experimental design:

  • DNA damage models: Induce double-strand breaks with etoposide in Bcl6⁻/⁻ vs. wild-type pre-B cells. Measure γH2AX foci and p53/Arf activation .

  • Co-factor recruitment: Perform PLA (Proximity Ligation Assay) to visualize BCL6 interactions with p300 or HDACs under genotoxic stress .

  • In vivo validation: Use Bcl6 conditional knockout mice to assess somatic hypermutation rates in GC B cells during antigen challenge .

Critical parameters:

  • Timing: Assess BCL6 dynamics within 4–6 hrs post-damage to capture early repair phases .

  • Dose titration: Optimize ERK inhibitor concentrations (e.g., SCH772984) to avoid off-target effects on parallel pathways .

What computational tools predict BCL6 phosphorylation crosstalk with other post-translational modifications?

Bioinformatics pipeline:

  • Motif analysis: Use ScanSite 4.0 to identify overlapping acetylation (e.g., Lys379) and phosphorylation sites .

  • MD simulations: Model structural changes in BCL6’s BTB domain upon Ser333 phosphorylation using AMBER or GROMACS .

  • Network modeling: Integrate PhosphoSitePlus data with STRING-db interactomes to map kinase-phosphatase regulatory loops .

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