Coding end processing is similar throughout ontogeny.

Abstract

During the recombination process, extensive processing of the coding ends provides tremendous potential diversity to the joint of any two gene segments. However, the diversity of the newborn B and T cell repertoires is greatly reduced compared with that of the adult. At the mechanistic level, this difference is primarily due to the absence of terminal deoxynucleotidyltransferase expression until the first week after birth. Additionally, one direct consequence of the lack of N regions early in ontogeny is the more frequent occurrence of homology-directed recombination, reducing even further the potential of diversity. Other enzymatic factors could also contribute to this ontogenic difference. However, the use of the homology-directed recombination pathway early in life obscures the analysis of the coding end processing. In this study we compared the coding end processing throughout ontogeny, in normal and terminal deoxynucleotidyltransferase -/- mice in the presence of minimal homology-directed recombination. The analysis of partial D-J joints allowed us to avoid potential bias by early selection events. Our results show that the extent of nucleotide deletion of a given end is consistent throughout ontogeny in the presence or absence of terminal deoxynucleotidyltransferase. However, a distinctive processing pattern is observed for each coding end.