IN INDIVIDUAL T CELLS ONE PRODUCTIVE a REARRANGEMENT DOES NOT APPEAR TO BLOCK REARRANGEMENT AT THE SECOND ALLELE
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چکیده
An individual B cell expresses only one functional light and one functional heavy chain on the cell surface. This process, termed allelic exclusion, arises as a consequence of the fact that the rearrangement of gene segments to assemble complete variable genes requires that only one functional VwDH:JH and one functional VL]L rearrangement occur in each B cell (1, 2). Presumably a VwDH:JH rearrangement that places the VH and ]H gene segments in the same translational reading frame (a productive rearrangement) on one chromosome precludes a subsequent V H to DH:J H rearrangement on the second heavy chain encoding chromosome. A similar mechanism seems to apply for the light chain (2). We have been interested in determining whether the antigen-binding receptors ofT cells also exhibit allelic exclusion at the level of DNA rearrangements. These TCRs are composed of a and~ chains that have variable and constant regions. The V a region, encoded by V a and ]a gene segments, and the V {J region, encoded by V fJ, Dp and Jp gene segments, also undergo rearrangement during T cell development (3). Our earlier studies of the ~ locus and recent transgenic experiments suggest that the ~ chain exhibits allelic exclusion in that a functionally rearranged V-D:J gene on one allele excludes subsequent V {J to Dp:JfJ rearrangements on the second allele ( 4, 5 ). The studies described below on the a loci of individual T cells suggest that they frequently give rise to two rearranged V a:la transcripts, one from each homologous chromosome.
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تاریخ انتشار 2003