Levels of polyadenylation factor CstF-64 control IgM heavy chain mRNA accumulation and other events associated with B cell differentiation

Cleavage stimulation factor (CstF) is one of the multiple factors required for mRNA polyadenylation. The concentration of one CstF subunit (CstF-64) i ncreases during activation of B cells, and this is sufficient to switch IgM heavy chain mRMA expression from membrane-bound form to secreted form. To extend this observation, we disrupted the endogenous CstF-64 gene in the B cell line DT40 and replaced it with a regulatable transgene. Strikingly, a 10-fold decrease in CstF-64 concentration did not markedly affect cell grow th bud specifically and dramatically reduced accumulation of IgM heavy chai n mRNA. Further reduction caused reversible cell cycle arrest: in G(0)/G(1) phase, while depletion resulted in apoptotic cell death. Our results indic ate that CstF-64 plays unexpected roles in regulating gene expression and c ell growth in B cells.