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[7] [17] [18] Although expression is typically found to be in the primary lymphoid organs, recent work has suggested that stimulation via antigen can result in secondary TdT expression along with other enzymes needed for gene rearrangement outside of the thymus for T-cells. [19] Patients with acute lymphoblastic leukemia greatly over-produce ...
V(D)J recombination (variable–diversity–joining rearrangement) is the mechanism of somatic recombination that occurs only in developing lymphocytes during the early stages of T and B cell maturation. It results in the highly diverse repertoire of antibodies/immunoglobulins and T cell receptors (TCRs) found in B cells and T cells, respectively.
T cells are grouped into a series of subsets based on their function. CD4 and CD8 T cells are selected in the thymus, but undergo further differentiation in the periphery to specialized cells which have different functions. T cell subsets were initially defined by function, but also have associated gene or protein expression patterns.
The RAG proteins initiate V(D)J recombination, which is essential for the maturation of pre-B and pre-T cells. Activated mature B cells also possess two other remarkable, RAG-independent phenomena of manipulating their own DNA: so-called class-switch recombination (AKA isotype switching) and somatic hypermutation (AKA affinity maturation). [2]
Generation of junctional diversity through recombination illustrated between two gene segments: D (blue) and J (green). Sections highlighted in red show nucleotides added at each stage. Junctional diversity describes the DNA sequence variations introduced by the improper joining of gene segments during the process of V(D)J recombination.
The purpose of thymocyte development is to produce mature T cells with a diverse array of functional T cell receptors, through the process of TCR gene rearrangement. Unlike most genes, which have a stable sequence in each cell which expresses them, the T cell receptor is made up of a series of alternative gene fragments.
The most common structural abnormality is the rearrangement of the T-cell receptor (TCR) gene. 95% of T-cell TCRs consist of an alpha and beta chain (encoded by TRA and TRB, respectively), while only 5% consist of gamma and delta chains (encoded by TRG and TRD, respectively). [4]
In both meiotic and mitotic cells, recombination between homologous chromosomes is a common mechanism used in DNA repair. Gene conversion – the process during which homologous sequences are made identical also falls under genetic recombination.