Question

Bcl-6 represses genes that function in lymphocyte differentiation, inflammation, and cell cycle con

Answer 1

BCL-6, a transcriptional repressor frequently translo- BCL-6-negative GC B cells include cells with plasmacytic morphology and may represent cells that are cated in lymphomas, regulates germinal center B cell terminally differentiating as they exit the GC (Falini et differentiation and inflammation. DNA microarray screen- al., 2000). Thus, plasmacytic differentiation, both pre- ing identified genes repressed by BCL-6, including and post-GC, occurs only in the absence of BCL-6 ex- many lymphocyte activation genes, suggesting that pression. BCL-6 modulates B cell receptor signals. BCL-6 re- Roughly one-sixth of all B cell non-Hodgkin’s lympho- pression of two chemokine genes, MIP-1a and IP-10, mas have translocations of the BCL-6 gene, making may also attenuate inflammatory responses. Blimp-1, BCL-6 one of the most frequently translocated genes another BCL-6 target, is important for plasmacytic dif- in these cancers (reviewed in Dalla-Favera et al., 1999; ferentiation. Since BCL-6 expression is silenced in Staudt et al., 1999). An attractive hypothesis is that plasma cells, repression of blimp-1 by BCL-6 may con- BCL-6 translocations cause non-Hodgkin’s lymphomas trol plasmacytic differentiation. Indeed, inhibition of by coopting BCL-6’s regulatory functions during B cell BCL-6 function initiated changes indicative of plas- differentiation. In keeping with this idea, the BCL-6 macytic differentiation, including decreased expres- translocations do not disrupt the BCL-6 coding region sion of c-Myc and increased expression of the cell but invariably substitute the BCL-6 promoter with a varicycle inhibitor p27kip1. These data suggest that malig- ety of other promoters. Thus, BCL-6 translocations likely nant transformation by BCL-6 involves inhibition of cause transformation of B cells by deregulating the exdifferentiation and enhanced proliferation.

Answer 2

Explanation:

BCL-6, a transcriptional repressor frequently translocated in lymphomas, regulates germinal center B cell differentiation and inflammation. DNA microarray screening identified genes repressed by BCL-6, including many lymphocyte activation genes, suggesting that BCL-6 modulates B cell receptor signals. BCL-6 repression of two chemokine genes, MIP-1α and IP-10, may also attenuate inflammatory responses. Blimp-1, another BCL-6 target, is important for plasmacytic differentiation. Since BCL-6 expression is silenced in plasma cells, repression of blimp-1 by BCL-6 may control plasmacytic differentiation. Indeed, inhibition of BCL-6 function initiated changes indicative of plasmacytic differentiation, including decreased expression of c-Myc and increased expression of the cell cycle inhibitor p27kip1. These data suggest that malignant transformation by BCL-6 involves inhibition of differentiation and enhanced proliferation.