VDJ recombination

VDJ Recombination

Background:

VDJ recombination occurs in the bone marrow (for B cells) and the thymus (for T cells) during lymphocyte development.

The process is mediated by a series of enzymes called recombinases, including the RAG1 and RAG2 proteins (Recombination-Activating Genes) in vertebrates.

Key Steps:

Diversity (D) Segment Selection: The process begins with the selection of one or more D segments from a pool of available D segments located within the gene locus encoding the antigen receptor.

Joining (J) Segment Selection: Next, a J segment is selected and brought into proximity with the selected D segment.

V(D)J Recombination: The RAG complex then catalyzes a DNA recombination event, whereby the selected D and J segments are cleaved and joined together, creating a rearranged V(D)J exon. This process is also referred to as "cut and paste" recombination.

V Segment Recombination: Finally, a V segment is selected and joined to the rearranged D-J segment, completing the assembly of the variable region of the antigen receptor.

Resulting Diversity:

The combinatorial joining of multiple V, D, and J gene segments generates a vast repertoire of antigen receptor diversity, enabling the immune system to recognize and respond to a wide range of foreign antigens.

Junctional diversity, arising from imprecise joining of the gene segments and the addition or deletion of nucleotides at the junctions, further increases receptor diversity.

Maturation and Selection:

Lymphocytes undergo further maturation and selection processes to ensure that they express functional antigen receptors capable of recognizing foreign antigens without reacting to self-antigens.

Cells that fail to generate functional receptors undergo programmed cell death (apoptosis), while those that successfully generate functional receptors proceed to further stages of development and differentiation.