BCL6


B-cell lymphoma 6 protein is a protein that in humans is encoded by the BCL6 gene. Like BCL2, BCL3, BCL5, BCL7A, BCL9 and BCL10, it has clinical significance in lymphoma.

Function

The protein encoded by this gene is an evolutionarily conserved zinc finger transcription factor and contains an N-terminal POZ/BTB domain. This protein acts as a sequence-specific repressor of transcription and has been shown to modulate the STAT-dependent Interleukin 4 responses of B cells. This protein can interact with several corepressor complexes to inhibit transcription. This gene is found to be frequently translocated and hypermutated in diffuse large B cell lymphoma and contributes to the pathogenesis of DLBCL. 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.
Physiologically, BCL6 is a master transcription factor which leads the differentiation of naive helper T cells in Follicular Helper T cells. Its action is negatively regulated by the gene PRDM1 encoding the transcription factor Blimp-1.

Diagnostic utility

The presence of BCL6 can be demonstrated in tissue sections using immunohistochemistry. It is exclusively present in the B-cells of both healthy and neoplastic germinal centres. It therefore demonstrates both reactive hyperplasia in lymph nodes and a range of lymphomas derived from follicular B-cells, such as Burkitt's lymphoma, follicular lymphoma and the nodular lymphocyte predominant subtype of Hodgkin's disease. It is often used together with antibodies to Bcl-2 antigen to distinguish neoplastic follicles from those found in benign hyperplasia, for which Bcl-2 is negative.

Interactions

BCL6 has been shown to interact with