Antibody function

Immunoglobulin specificity derives from V(D)J exon variation

Biological systems exploit variability. Bacteria and viruses, for example, use genetic variability to acquire resistance to host defense mechanisms. The human immune system deploys similar strategies to counter the threat posed by these noxious moving targets. There are two main mechanisms by which immunocytes generate antibody diversity:

1. 1. Germline V(D)J recombination.

2. 2. Somatic hypermutation.

Immunoglobulins are multisubunit proteins consisting of two heavy chains (each containing about 440 amino acids) and two light chains (each about half the size of a heavy chain). These subunits are encoded by genes at three loci: the κ light chain locus on chromosome 2; the λ light chain locus on chromosome 22; and the heavy chain locus on chromosome 14. Transcription of these genes is controlled by transactivating molecules that bind enhancers present within the respective genomic DNA sequences.

Light chains consist of constant (C), variable (V), and joining (J) domains, whereas heavy chains contain an additional diversity (D) chain. The tremendous range of immunoglobulin variation arises due to V(D)J exon recombination within these latter gene loci. As the name suggests, the constant (C) domain does not undergo recombinational modification.