Immune genes as substrates for recombination

The unrearranged immune receptor genes (immunoglobulin and T cell receptor) share the same basic organization - the genes are discontiguous. The chains of the immunoglobulin and T cell receptor (TCR) molecules are encoded as small segments (V, D, J and C) that must associate with each other to provide the complete coding sequence. The genes for the immunoglobulin heavy chain and for the light chains k and X are located on chromosomal bands 14q32, 2pl2 and 22qll, respectively. The TCR genes are encoded on 7pll (TCRy), 7q34 (TCRfJ) and 14ql 1 (TCRa and TCR8).

Recombinational pathway in the rearrangement of immune genes

During the process of generating a functional heavy chain, the intervening genomic DNA between the randomly selected D (diversity) and J (joining) segments is excised, bringing together the DH and the JH segments. This process is thought to occur simultaneously on both alleles. Following this rearrangement, a V (variable) region on one of the alleles is approximated to the DJ region to form the VDJ exon. The coupling of the VDJ regions is an imprecise mechanism which includes the insertion of a few extra nucleotides (N) and may result in an 'out-of-frame' rearranged gene. If so, the V region on the second allele is allowed to recombine to give the B cell a second chance to generate a productive allele, before undergoing apoptosis. The light chain and the TCR genes go through a similar VJ/VDJ rearrangement.

Normally, the mechanism of recombination necessary for the production of an immunoglobulin or a T cell receptor molecule allows intralocus recombination to assemble the VDJ regions of the immune genes. In B cells an additional recombination path-

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