V(D)J recombination

The V (D) J recombination (also known as somatic recombination) is a genetic rearrangement process in vertebrates, of the variability of antibodies (immunoglobulins, also: B -cell receptor ), produced by B- cells and T- cell receptors provides. It plays a crucial role in the adaptive immune system by recognizing a variety of antigens of bacterial, viral or parasitic origin is possible.

It is worth mentioning that this is the only known process in which the genetic information (DNA) in somatic, proliferating cells schedule, so to speak, deliberately ' changed.

Function

It is a recombination, in which the different DNA fragments of the genes for the light and heavy chains of the antibody and T- cell receptors are randomly combined.

The variable portions of both chains (V- regions) are made up of different sections. These are the V segments and J segments in the case of the light chains and in addition to these two, the D segments in the case of the heavy chains. Of each segment in the genome, there are several variants, one of which is in each case later on in the final batt. This recombination occurs only once per cell, and it is left to chance, which allele, ie which gene on homologous chromosomes ( mother or father), is first recombined. The recombination of an allele inhibited in case of success (see below), the processing of the second allele ( " allelic exclusion ").

Additional variability arises from the combination of light and heavy chains and junctional diversification. Ultimately (no junctional diversity and somatic hypermutation ) approximately 1.92 million possible combinations for the formation of immunoglobulins present.

Genetic background

The immunoglobulins produced by a B cell consist fundamentally of two identical long ( heavy, Eng. Heavy) H chains and two identical short ( lightweight, Eng. Light) L chains ( κ or λ chain). These chains each have a constant ( C ) and variable (V ( D) J ) share.

κ or λ locus differ in the arrangement of the V, J and C segments: While in the κ locus V and J segments in clusters ( C- there is only one segment), there are λ JC locus four pairs. The heavy-chain locus is similar in organization to the κ locus, but contains a plurality of carbon segments and between the V and J a D - cluster clustering. In all cases, each V segment is an L- segment ( leader) preceded by representing the signal sequence for translocation into the rough endoplasmic reticulum.

T-cell receptor is comprised of α and β - chain, the former is similar to the light chain of the immunoglobulins, the latter a fragment ( Fab fragment) of the heavy chain.

The locus refers to the people.

The name V (D) J recombination is derived here from the English name for each recombined gene segments from (V - variable, D - diversifying, J - joining ). In addition, in any case still a C region (C - constant). While the variable region determines the antigen recognition, while the constant region determines the five immunoglobulin classes and is responsible for membrane anchoring the T cell receptor.

The large repertoire of immunoglobulins and T- cell receptor specificities that would blow up the size of the genome, unless a specific gene would be present for each molecule is realized, among other things, that the individual gene segments (V, D, J) before the rearrangement in multiple copies exist, which can be combined with each other during the maturation of lymphocytes in the manner of a combination lock.

In addition, there are a number of pseudogenes that are available for the rearrangement are available, but can not form a functional chain.

Expiration

Immunoglobulins

In the rearrangement of the heavy chain the combination of a first and of a D- J segment takes place before these are attached to a V segment to form a joint with this exon. In the case of the light chain (without D segment ) can be done immediately combining V and J segments. The thus produced V region is separated by an intron of the C-region, merging thus takes place after transcription by splicing.

The Rekombinationsstatus is a criterion for determining the stage of B cell maturation.