The Regulation of Expression of Terminal Deoxynucleotidyl Transferase in an Inducible Murine Pre-B Cell Line

Abstract:

The purpose of this study was to understand the control of synthesis of Tdt at a molecular level, using a murine pre B-cell line inducible for the enzyme. FLEl-4, an Abelson virus transformed fetal liver cell line, when treated with dibutyryl cAMP and caffeine (or other phosphodiesterase inhibitors), shows a three- to tenfold induction of Tdt, as measured by immunoprecipitation of pulse labelled enzyme, activity assays, and steady-state northern blot. The study also revealed Tdt expression (mRNA induction) by a group of agents which inhibit DNA synthesis by various mechanisms.

This finding implies that Tdt expression is unlinked to clonal proliferation of pre-B cells, and suggests a multistage model for B-cell differentiation and the generation of immunoglobulin somatic variation. At a molecular level, the agents that induce Tdt were also shown to increase intracellular cAMP levels shortly before Tdt transcription. Finally, an analysis of histone phosphorylation patterns in induced cells reveal a marked enhancement of histone HI phosphorylation, a finding which may be related to the induction event.

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