PJA-BP expression and TCR delta deletion during human T cell differentiation |
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Authors: | Verschuren MC; Blom B; Bogers AJ; Spits H; van Dongen JJ |
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Institution: | Department of Immunology, Erasmus University Rotterdam and University Hospital Rotterdam, The Netherlands. |
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Abstract: | Recombination of deltaRec to psiJalpha will delete the TCR delta gene,
which is thought to play an important role in the bifurcation of the TCR
alphabeta versus TCR gammadelta differentiation lineages. We recently
detected a DNA-binding protein in human thymocytes, the so- called PJA-BP,
which recognizes the psiJalpha gene segment and might be one of the factors
involved in the regulation of preferential deltaRec- psiJalpha
rearrangements. We now investigate PJA-BP expression and its correlation
with TCR delta gene deletion in thymocytes. Our electrophoretic mobility
shift assay experiments showed that the PJA-BP is evolutionary conserved in
human, murine and simian thymocytes. Using a large series of human
hematopoietic malignancies (n = 30), we conclude that PJA-BP expression is
thymocyte specific and seems to be restricted to thymocytes committed to
the TCR alphabeta lineage. Analysis of seven well-defined human thymocyte
subpopulations showed that preferential deltaRec-psiJalpha rearrangements
as well as PJA-BP expression can be detected from the immature
CD34-/CD1+/CD3- /CD4+/CD8alpha+beta- thymocyte differentiation stage
onwards. These experiments indicate that expression of PJA-BP in human
thymocytes starts simultaneously with preferential deltaRec-psiJalpha
rearrangements, which supports our hypothesis that PJA-BP is one of the
factors involved in the preferential recombination of deltaRec to
psiJalpha.
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