Figure 2.

Recombination of immunoglobulin V (variable), D (diversity), and J (joining) segments of immunoglobulin heavy and light chains. (A) Tertiary structure of an antibody indicating two molecules of immunoglobulin heavy (IgH) and light chains (IgL). Each IgH is composed of a variable region (VH) derived from the V(D)J segments of the IgH gene and constant (CH) regions. On the other hand, IgL is composed of a variable region (VL) derived from recombining V and J segments of the IgL gene and smaller constant regions (CL). (B) Sequence of immunoglobin gene segment recombination. (C) The IgH gene is composed of V, D, and J gene segments that are flanked by recombination signal sequences (RSS) that are 23 or 12 nucleotides long. In the first step of IgH recombination, D and J segments access is enabled by unwinding of DNA in these regions by e.g. HMG proteins enabling the binding of a complex of recombination-activating genes 1 and 2 (RAG1/2) randomly to any of these segments. Endonuclease activity by RAG1/2 enables removal of intervening sequences, formation of DNA hairpins and recruitment of the non-homologous end joining DNA repair machinery. Here, hairpins are opened by the activity of Ku70/80, Artemis and DNA PKC complexes while ends are ligated by the activity of XRCC4 and DNA ligase IV.