Common mechanisms for the regulation of B cell differentiation and transformation by the transcriptional repressor protein BCL-6.

The BCL-6 transcriptional repressor protein is a critical regulator of normal B cell differentiation and BCL-6 has recently been shown to act as an oncogene in several mouse model systems. The molecular pathways by which BCL-6 regulates B cell differentiation and also promotes the transformation of primary B cells are undoubtedly related; however, these pathways are poorly understood. The commonly accepted model for BCL-6 function in B cells is that BCL-6 inhibits the terminal differentiation of activated B cells into plasma cells and that deregulation of BCL-6 expression leads to an inhibition of terminal differentiation and continued proliferation. BCL-6 induces a germinal-center phenotype in primary B cells by unknown mechanisms, and can reverse the terminal differentiation of plasma cell tumor lines. BCL-6 can promote the immortalization of primary B cells and can augment telomerase activity. The role of the vast majority of BCL-6 target genes and interacting proteins in normal B cell differentiation and B cell transformation is essentially unresolved and is an important area for future investigation.