V(D)J Recombination - Background

Background

Human antibody molecules (and B cell receptors) are composed of heavy and light chains with both constant (C) and variable (V) regions that are encoded by genes on three loci.

  1. Immunoglobulin heavy locus (IGH@) on chromosome 14, containing genes for the immunoglobulin heavy chain
  2. Immunoglobulin kappa (κ) locus (IGK@) on chromosome 2, containing genes for the immunoglobulin light chain
  3. Immunoglobulin lambda (λ) locus (IGL@) on chromosome 22, containing genes for the immunoglobulin light chain

Multiple genes for the variable regions are encoded in the human genome that contain three distinct types of segments. For example, the immunoglobulin heavy chain region contains 44 Variable (V) genes plus 27 Diversity (D) genes and 6 Joining (J) genes. The light chains also possess numerous V and J genes, but do not have D genes. By the mechanism of DNA rearrangement of these regional genes it is possible to generate an enormous antibody repertoire; roughly 3×1011 combinations are possible, although some are removed due to self reactivity.

Most T cell receptors are composed of an alpha chain and a beta chain. The T cell receptor genes are similar to immunoglobulin genes in that they too contain multiple V, D and J genes in their beta chains (and V and J genes in their alpha chains) that are rearranged during the development of the lymphocyte to provide that cell with a unique antigen receptor.

Failure of the cell to create a successful product that does not self-react leads to cell apoptosis.

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