The level of N-region diversity in T cell receptors is not pre-ordained in the stem cell.
The alpha beta T cell repertoires of adults and neonates are distinctly different. For example, T cell receptors (TcR) from adult animals have substantial N-nucleotide addition at their V-D-J junctions while those from neonatal animals do not. This dichotomy reflects a rather abrupt change in expression of the terminal deoxynucleotidyl transferase (TdT) gene in thymocytes on day 4 after birth. We have asked whether this change is due to the differentiation of successive waves of stem cells harboring different potentials for TdT expression, a scenario like the one proposed to explain developmental regulation of gamma delta T cell repertoires. Reconstitution of adult severe combined immunodeficiency mice with either fetal liver or adult bone marrow precursors gave rise to T cells with substantial N-region diversity in their TcR, even at the earliest points of reconstitution. It is most likely, then, that the abrupt change in TdT gene expression in day 4 thymocytes is due to an environmentally induced switch-on.
Bogue
M
M
LGME du CNRS, U. 184 de Biologie Moléculaire et de Génie Génétique de l'INSERM, Faculté de Médecine, Strasbourg, France.
Mossmann
H
H
Stauffer
U
U
Benoist
C
C
Mathis
D
D
D000818:Animals; D001483:Base Sequence; D004253:DNA Nucleotidylexotransferase / Q000235:genetics; D005260:Female; D015329:Gene Rearrangement, T-Lymphocyte; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D016219:Immunotherapy, Adoptive; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D008969:Molecular Sequence Data; D011247:Pregnancy; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*
D011948:Receptors, Antigen, T-Cell; D004253:DNA Nucleotidylexotransferase