DOWN-REGULATION OF TERMINAL DEOXYNUCLEOTIDYL TRANSFERASE BY IG HEAVY-CHAIN IN B-LINEAGE CELLS

The enzyme terminal deoxynucleotidyl transferase (TdT) adds nontemplat e-derived nucleotides (N regions) to the junctions between recombining variable, diversity, and joining segments of Ig genes, The relative p aucity of N regions in Ig light chains, together with the down-regulat ion of TdT transcription in pre-B cells (prior to light chain producti on), suggested that production of IgM heavy chain (mu) protein might n egatively regulate TdT expression. In this study, we examined the effe ct of mu. production on TdT gene expression in B lineage subsets from normal mice, from recombination-deficient mice (SCID and Rag-1(-)) car rying mu transgenes, and in transformed pro-B cell lines transfected w ith mu constructs. In normal mice, TdT is sharply down-regulated at th e early pre-B stage in which cells have just completed productive mu r earrangement. Furthermore, the expression of mu. transgenes in pro-B s tage cells from recombination-deficient mice results ina similar decre ase. Finally, transfection of genomic constructs encoding mu into pro- B cell lines results in a marked reduction of TdT expression. Taken to gether, these findings indicate that mu protein production results in the down-regulation of TdT. The ability of mu transgenes to alter TdT expression in cell lines also suggests that signaling through the pre- B receptor does not necessarily require interaction with an external s tromal cell-derived ligand.