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TE Hansen-Hagge, C Mahotka, RE Panzer-Grumayer, HJ Reuter, K Schwarz, JJ van Dongen and CR Bartram
Department of Pediatrics II, University of Ulm, Germany.
Lymphocytes expressing alpha beta or gamma delta T-cell receptors (TCR)
represent distinct T-cell populations. Because TCR delta genes lie within
the TCR alpha locus, the rearrangement processes, transcription, and
translation of TCR delta or TCR alpha variable domain exons require tight
regulation. Human precursor B-cell leukemias (eg, the REH cell line)
constitute an interesting model to study TCR delta/alpha recombination
because they rearrange TCR delta/alpha loci along a hierarchically ordered
pathway in which V delta 2D delta 3 segments are joined to the J alpha
cluster. We now show for REH cells that chimeric TCR delta/alpha variable
domain exons are posttranscriptionally modified by alternative splicing
resulting in truncated V delta 2C alpha transcripts. This process also
takes place during thymic differentiation. CD7+/CD3- T-cell precursors
exhibit V delta 2D delta 3 rearrangements. Further differentiation into
CD7+/CD3+ thymocytes is associated with the expression of a truncated V
delta 2C alpha RNA species. In contrast, chimeric TCR delta/alpha
rearrangements containing a V delta 1 segment (but no D delta sequences)
are predominantly expressed as full-length V delta 1J alpha C alpha
transcripts. These data suggest that alternative splicing constitutes a
mechanism that restricts the production of distinct chimeric TCR alpha
chains.
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| Copyright © 1995 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||