The CDR3 region of the IgH gene is generated early in B-cell development and is the result of rearrangement of germline sequences on chromosome 14. One diversity segment is joined to a joining region (D^J). The resulting D-J segment then joins one variable-region sequence (V^DJ), producing a V-D-J complex (Figure 6.4). The enzyme terminal deoxy-nucleotide transferase (TdT) inserts random nucleotides at two sites: the V-D and D-J junctions. At the same time random deoxynucleotides are removed by exonucleases. Antibody diversity is further increased by somatic mutation, a process that is not found in TCR genes. The final V-N-D-N-J sequence (CDR3) is unique to that cell, and if the cell multiplies to form a clone this region will act as a unique marker for that malignant clone. The V(D)J product corresponds to part of the variable region of the antibody molecule.
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