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Hub AI
BCL6 AI simulator
(@BCL6_simulator)
Hub AI
BCL6 AI simulator
(@BCL6_simulator)
BCL6
Bcl-6 (B-cell lymphoma 6) is a protein that in humans is encoded by the BCL6 gene. BCL6 is a master transcription factor for regulation of T follicular helper cells (TFH cells) proliferation. BCL6 has three evolutionary conserved structural domains. The interaction of these domains with corepressors allows for germinal center development and leads to B cell proliferation.
The deletion of BCL6 is known to lead to failure of germinal center formation in the follicles of the lymph nodes, preventing B cells from undergoing somatic hypermutation. Mutations in BCL6 can lead to B cell lymphomas because it promotes unchecked B cell growth. Clinically, BCL6 can be used to diagnose B cell lymphomas and is shown to be upregulated in a number of cancers.
Other BCL genes, including BCL2, BCL3, BCL5, BCL7A, BCL9, and BCL10, also have clinical significance in lymphoma.
The protein encoded by the BCL6 gene is a zinc finger transcription factor that has three evolutionarily conserved domains. BCL6 contains a (1) N-terminal BTB/POZ domain (Broad-complex, Tramtrack and Brick-a-brac/Pox virus and Zinc finger family domain), (2) a central RN2 region, and (3) another zinc finger at the C-terminal end. This structure is vital to BCL6’s function – an exon 7 skipping splice variant encodes a shorter form of the protein which lacks the first two zinc fingers of the DNA binding domain, for example.
Bcl-6 is a master transcription factor for the regulation of T follicular helper cells (TFH cells). Bcl-6 is expressed when the cytokines Il-6 and/or Il-21 are recognized; these cytokines can be produced by antigen presenting cells (APCs: B cells, dendritic cells, or macrophages) when activated. This occurs when a naïve T helper cell recognizes antigen and needs to migrate to the follicle as a T follicular helper cell (TFH cell). TFH cells are vital to the generation of germinal centers in the follicles of secondary lymphoid organs, where B cells divide and help fight infections.
As a master transcription factor, BCL6 interacts with a variety of co-repressors and other proteins to influence the T cell lineage. BCL6 has been shown to modulate the STAT-dependent Interleukin 4 (IL-4) responses of B cells[citation needed] and suppress the production of BCL2.
Importantly, Bcl-6 should only be expressed when there is an antigen present and further stimulation of the immune system is necessary, since BCL6 prevents cell death (apoptosis). Unchecked growth can lead to lymphomas. Normally, the action of BCL6 is negatively regulated by the gene PRDM1 encoding the transcription factor Blimp-1. The antagonistic effect with Blimp-1 is a powerful role of BCL6, because it shuts off the normal pathway of differentiation toward other cell types.
BCL6 is currently considered a lineage-defining transcription factor in TFH cell differentiation. Without the expression of BCL6, naïve CD4+ T helper cells will not turn into TFH cells. When a naïve CD4+ T cell binds to MHC class II and an antigen peptide on a dendritic cell, a signaling cascade ensues in which some proliferating T cells become TFH cells. Signaling through the IL-6 receptor leads to TFH cell differentiation, and in turn the expression of BCL6 in TFH lineage-defined cells. BCL6 allows, through transcriptional regulation, unique cell markers to be expressed, resulting in an effective TFH cell.
BCL6
Bcl-6 (B-cell lymphoma 6) is a protein that in humans is encoded by the BCL6 gene. BCL6 is a master transcription factor for regulation of T follicular helper cells (TFH cells) proliferation. BCL6 has three evolutionary conserved structural domains. The interaction of these domains with corepressors allows for germinal center development and leads to B cell proliferation.
The deletion of BCL6 is known to lead to failure of germinal center formation in the follicles of the lymph nodes, preventing B cells from undergoing somatic hypermutation. Mutations in BCL6 can lead to B cell lymphomas because it promotes unchecked B cell growth. Clinically, BCL6 can be used to diagnose B cell lymphomas and is shown to be upregulated in a number of cancers.
Other BCL genes, including BCL2, BCL3, BCL5, BCL7A, BCL9, and BCL10, also have clinical significance in lymphoma.
The protein encoded by the BCL6 gene is a zinc finger transcription factor that has three evolutionarily conserved domains. BCL6 contains a (1) N-terminal BTB/POZ domain (Broad-complex, Tramtrack and Brick-a-brac/Pox virus and Zinc finger family domain), (2) a central RN2 region, and (3) another zinc finger at the C-terminal end. This structure is vital to BCL6’s function – an exon 7 skipping splice variant encodes a shorter form of the protein which lacks the first two zinc fingers of the DNA binding domain, for example.
Bcl-6 is a master transcription factor for the regulation of T follicular helper cells (TFH cells). Bcl-6 is expressed when the cytokines Il-6 and/or Il-21 are recognized; these cytokines can be produced by antigen presenting cells (APCs: B cells, dendritic cells, or macrophages) when activated. This occurs when a naïve T helper cell recognizes antigen and needs to migrate to the follicle as a T follicular helper cell (TFH cell). TFH cells are vital to the generation of germinal centers in the follicles of secondary lymphoid organs, where B cells divide and help fight infections.
As a master transcription factor, BCL6 interacts with a variety of co-repressors and other proteins to influence the T cell lineage. BCL6 has been shown to modulate the STAT-dependent Interleukin 4 (IL-4) responses of B cells[citation needed] and suppress the production of BCL2.
Importantly, Bcl-6 should only be expressed when there is an antigen present and further stimulation of the immune system is necessary, since BCL6 prevents cell death (apoptosis). Unchecked growth can lead to lymphomas. Normally, the action of BCL6 is negatively regulated by the gene PRDM1 encoding the transcription factor Blimp-1. The antagonistic effect with Blimp-1 is a powerful role of BCL6, because it shuts off the normal pathway of differentiation toward other cell types.
BCL6 is currently considered a lineage-defining transcription factor in TFH cell differentiation. Without the expression of BCL6, naïve CD4+ T helper cells will not turn into TFH cells. When a naïve CD4+ T cell binds to MHC class II and an antigen peptide on a dendritic cell, a signaling cascade ensues in which some proliferating T cells become TFH cells. Signaling through the IL-6 receptor leads to TFH cell differentiation, and in turn the expression of BCL6 in TFH lineage-defined cells. BCL6 allows, through transcriptional regulation, unique cell markers to be expressed, resulting in an effective TFH cell.
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