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Figure 16.1 Organization of gene loci of immunoglobulin gene:

16.2 Mechanism of V (D) J recombination

The recombination of V, (D), and J chains is a type of non homologous recombination which is mediated by many enzymes including DNA double stranded break repair (DSBR) enzymes. The whole process is divided into four distinct phases.

Synapsis

Cleavage

Hairpin-opening and processing of ends

Joining

16.2.1 Synapsis

This is the process by which the antigen receptor genes are made accessible for the recombination machinery. The selected regions are brought together by looping of the chromosome for subsequent processes.

16.2.2 Cleavage

DNA in the specific region is broken with the help of recombination activating gene-1 (Rag-1) and Rag-2 to bring the RSS-coding sequence closer. The Rag-1/Rag-2 complex is known as V (D) J recombinase. Rag-1 acts as a restriction endonuclease to recognize and cleave the heptamer sequences. Rag-2 protein helps to bring the Rag-1/Rag-2 tetramer complex together. Rag genes are only expressed in lymphoid origin cells i.e. B and T lymphocytes.