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.
Kusam
Saritha
S
Department of Microbiology and Immunology and The Walther Oncology Center, Indiana University School of Medicine, 950 W. Walnut St. R2 302, Indianapolis, IN 46202, USA.
Dent
Alexander
A
D000818:Animals; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000166:cytology / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology*; D002471:Cell Transformation, Neoplastic; D004789:Enzyme Activation; D006801:Humans; D008223:Lymphoma / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D051560:Proto-Oncogene Proteins c-bcl-6 / Q000502:physiology*; D015398:Signal Transduction; D019098:Telomerase / Q000378:metabolism
D051560:Proto-Oncogene Proteins c-bcl-6; D019098:Telomerase