The proto-oncogene Bcl6 inhibits apoptotic cell death in differentiation-induced mouse myogenic cells

Abstract

The Bcl6 gene is located at chromosomal band 3q27, a breakpoint for translocation that frequently occurs in B cell lymphomas. Bcl6 has been found to be preferentially expressed in germinal center B cells, and expression of this gene has been shown to be essential for germinal center formation in vivo. The physiological function of Bcl6 and its role in lymphomagenesis, however, are not yet known. Since significant expression of Bcl6 has been demonstrated in skeletal muscle, we have utilized a differentiation-inducible mouse myogenic cell line, C2C12, to elucidate the function of the Bcl6 gene product. Expression of Bcl6 mRNA was very low in growing myocytes, but was increased in differentiating myocytes cultured in serum-starved medium. Incubation of these cells with cytokines or chemicals that are known to block differentiation suppressed this increased Bcl6 message abundance, indicating that Bcl6 induction is related to the process of terminal differentiation in muscle cells. While a fraction of myocytes is known to undergo apoptosis after serum-starvation to induce differentiation, adenovirus-mediated overexpression of Bcl6 enhanced the viability of the differentiating cells by preventing the apoptosis. High levels of Bcl6 antisense mRNA expression induced substantial apoptosis during the differentiation of C2C12 cells, but this was effectively prevented by infection with adenovirus that expressed Bcl6 sense mRNA. These results indicate that Bcl6 acts to prevent apoptotic cell death in differentiating myocytes. The deregulation of expression of this anti-apoptotic gene may also contribute to the development of B cell lymphomas.