T-cell receptor J beta gene segment usage in immature and mature human thymocytes.
Immature double positive (DP, CD4+CD8+) and mature single positive (SP, CD4+CD8- and CD4-CD8+) human thymocytes from nine thymi were analysed for their complete patterns of relative TCR J beta multigene member usage in relation to six rearranged V beta family exons (V beta 5.1, 6.1-3, 8, 9, 12 and 18). Each sample tested contained mRNA transcripts corresponding to all potential V beta(D beta)J beta combinations. Individual J beta gene segments were expressed in a similar, highly non-random manner both in SP and DP thymocytes, irrespective of original genomic position of the individual associated V beta exon. In addition, ranges of family usage and frequency of individual over-representations of J beta gene segments, as determined in DP and SP thymocyte populations, displayed no significant differences. Upon comparison of DP and SP thymocytes, however, a discrepancy in one aspect of J beta gene utilization was established: decreasing J beta family 1/J beta family 2 ratios were determined to be positively correlated with increasing maturity of thymocytes, a condition further supported by data previously obtained from studies of PBL T cells. At the individual J beta gene level, the observed gradual modification of the relative family usage can largely be explained by a significant shift from a higher J beta 1.1/J beta 2.7 ratio in DP to a higher J beta 2.7/J beta 1.1 ratio in SP thymocytes. Altogether, the present results imply that selectional processes in the thymus appear to have only minor consequences on the distribution pattern of expressed J beta exons. Hence, the disproportionate pattern of TCR J beta gene usage seems to be established mainly at the recombinatorial level followed by minor adjustments during thymic and post-thymic events.
Jeddi-Tehrani
M
M
Microbiology and Tumorbiology Center, Karolinska Institute, Stockholm, Sweden.
Hodara
V
V
Esin
S
S
Grunewald
J
J
Wigzell
H
H
Andersson
R
R
D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002675:Child, Preschool; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000235:genetics* / Q000276:immunology; D007223:Infant; D011948:Receptors, Antigen, T-Cell / Q000235:genetics* / Q000276:immunology; D013950:Thymus Gland / Q000276:immunology*
D007135:Immunoglobulin Variable Region; D011948:Receptors, Antigen, T-Cell