Pluripotent bone marrow stem cells give rise to progenitor T cells, which migrate to the thymus for primary ontogeny. There, TCR genes undergo somatic rearrangement of germline gene sequences, similar to the process that occurs in immunoglobulin heavy (IGH) and light-chain (IGLK and IGLL) genes. The four TCR genes are rearranged in the following order: TCRD (on chromosome 14q11), TCRG (7p15), TCRB (7q34),and TCRA (14q11).' These rearrangements occur early in T-cell development and are unique to each cell, ensuring great receptor diversity (Figure 33-1). The genetic recombination occurs when the variable (V) segments are joined with a diversity (D) region (present only in the TCRB and TCRD genes) or with a joining (J) region by deletion of the intervening coding and noncod-ing DNA sequences. Thus, the TCRB and TCRD gene rearrangements result in V-D-J juxtaposition similar to the IGH gene, whereas the TCRA and TCRG genes contain only V-J rearrangements. In all cases, the V-(D)-J segment is apposed to the downstream constant (C) region by mRNA splicing (Figure 33-2). The TCR genes are translated into two types of receptors, which exist as heterodimers (aP or y5).2 Approximately 95% of mature, circulating T cells express the aP receptor because the initial 5 or y rearrangements failed to produce a functional receptor. In the skin, spleen, gastrointestinal tract, and other extranodal sites, y5 T cells are more commonly identified. T-cell neoplasms ensue after maturation arrest at one of the stages of T-cell development (Figure 33-1). They can originate from immature T cells as in lymphoblastic T-cell lymphoma, or from more mature T cells, as seen in peripheral T-cell lymphoma
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