Down-regulation of terminal deoxynucleotidyl transferase by Ig heavy chain in B lineage cells.
The enzyme terminal deoxynucleotidyl transferase (TdT) adds nontemplate-derived nucleotides (N regions) to the junctions between recombining variable, diversity, and joining segments of Ig genes. The relative paucity of N regions in Ig light chains, together with the down-regulation of TdT transcription in pre-B cells (prior to light chain production), suggested that production of IgM heavy chain (mu) protein might negatively regulate TdT expression. In this study, we examined the effect of mu production on TdT gene expression in B lineage subsets from normal mice, from recombination-deficient mice (SCID and Rag-1-) carrying mu transgenes, and in transformed pro-B cell lines transfected with mu constructs. In normal mice, TdT is sharply down-regulated at the early pre-B stage in which cells have just completed productive mu rearrangement. Furthermore, the expression of mu transgenes in pro-B stage cells from recombination-deficient mice results in a similar decrease. Finally, transfection of genomic constructs encoding mu into pro-B cell lines results in a marked reduction of TdT expression. Taken together, 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 stromal cell-derived ligand.
Wasserman
R
R
Division of Oncology, The University of Pennsylvania School of Medicine, Philadelphia 19104, USA.
Li
Y S
YS
Hardy
R R
RR
D000818:Animals; D001402:B-Lymphocytes / Q000201:enzymology*; D001854:Bone Marrow Cells; D004253:DNA Nucleotidylexotransferase / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D015322:Gene Rearrangement, B-Lymphocyte; D018398:Homeodomain Proteins; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008817:Mice, Mutant Strains; D016513:Mice, SCID; D008822:Mice, Transgenic; D011506:Proteins / Q000502:physiology
D018398:Homeodomain Proteins; D007143:Immunoglobulin Heavy Chains; D011506:Proteins; C064658:RAG-1 protein; D004253:DNA Nucleotidylexotransferase