Detecting Monoclonal Immunoglobulin andT-Cell Receptor Gene Rearrangements in B- andT-Cell Malignancies by Polymerase...

B cells undergo gene rearrangement of one of their immunoglobulin heavychain genes at an early stage in B-cell development. During rearrangement of the immunoglobulin heavy-chain gene (IgH), a variable gene segment (V) is joined to a diversity gene segment (D), and then subsequently this complex is recombined to a joining gene segment (J). Nucleotides are added and removed at random at the V-D and D-J junctions (1). Similarly, early in development of T cells, the T-cell receptor (TCR) genes rearrange. In the case of the T-cell receptor γ (TCRγ) gene, the V-gene segment is brought into juxtaposition of a J-gene segment. Nucleotides are then added and deleted at random at the V-J junction (2). It is these gene rearrangements that are responsible for the immune repertoire. Usually only one of the chromosomes will rearrange and the other remains in the germ-line configuration. Although, if the first rearrangement is ineffective then the other chromosome may rearrange. The IgH and TCRγ rearrangements will vary in DNA sequence and usually in size between lymphocyte clones and a normal individual will have a very large number of different IgH or TCRγ rearrangements.