Recombination V (D) J

The recombination V (D) J is a mechanism of recombination of DNA present at the human ones and the other vertebrate ones. It is a site-specific reaction of recombination which makes it possible to create a great diversity of TCR and of Immunoglobuline S which is necessary to the recognition of the immense variety of the foreign antigens. It is a key phenomenon in defense against pathogenic bacterial, viral and parasitic ones.

Recombination V (D) J

Recombination VDJ of Immunoglobulins

The Anticorps are composed of chains of proteins door and light, each type containing a constant part (C) and one variable part (V). The genes coding these light or heavy chains are located has various places of the genome.

heavy Chain, gene located on the chromosome 14
light Chaîne kappa (κ), gene located on chromosome 2
light Chaîne lambda (λ), gene located on the chromosome 22

NB: there are thus two copies of each gene, since the human genome is Diploïde.

The areas V are coded by genes which comprise standard trios of segments. For example, the gene of the heavy chain contains 200 genes Variables (V), 12 genes of Diversity (D) and 4 genes of Junction (J). The genes coding the light chains also have many segments V and J, but no genes D. the recombination between fragments VDJ thus makes it possible to generate >10⁷ possible combinations (200 X 12 X 4 = 9600 combinations for the heavy chain, approximately 1000 for the light chains.

In the lymphocytes B under development, the first recombination to take place is done between a segment D and a segment J of a locus of heavy chain. All the chain of DNA located between these two segments is eliminated. This recombination D-J is followed by the junction of a segment V coming from a locus upstream of gene DJ lately formed. This time still, all the locus located before between the segment V and the DJ is eliminated from the genome. At the time of the transcription of gene, ARN messenger contains area VDJ recombinee heavy chain, as well as the constant segments driven and delta (C_μ and C_δ). This first transcribes sudden traditional post-transcriptionelles modifications (Polyadenylation, epissage of the Intron S) and an alternate épissage leading genes coding the constant segments. The Traduction of this ARNm produces the heavy chain Ig μ.

The loci of genes coding the light chains kappa (κ) and lambda (λ) rearrange in a very similar way, has this close the light chains are deprived of segment D. In other words, the first stage of the recombination of the light chains relates to the segments V and J to form a complex VJ, before the addition of the constant segment of the light chain at the time of the transcription. The translation of spliced ARNm of the chains kappa or lambda produces light chains Ig κ or Ig λ.

The assembly of two heavy chains Ig μ and two chains light leads to the formation of the membrane shape of the immunoglobulin IgM expressed on the surface of the lymphocytes B, the BCR (B-concealment receptor). The assembly of a light chain with a heavy chain forms a single Paratope; each Ig is thus bivalent.

Remarks

the formation of immunoglobulins of others Isotype S is related on the isotypic Commutation, and not to recombination VDJ.
the " term; immunoglobuline" recover proteins here constituting BCR as well as the various types of antibody. It is not a question of the " imunoglobuline" field;.

Recombination VDJ of TCR

The majority of the T-concealment receptor are hétérodimères forms starting from a chain alpha and of a chain beta. The genes coding proteins of the TCR are structurally similar has those of immunoglobulins. They contain many fields V, D and J for the chains beta, and only V and J for the chains alpha. These loci is rearranged during the development of the lymphocytes T, which gives them their antigenic specificity.

During the development of the lymphocytes T, the genes coding the sub-units constituting TCR recombine according to the same model as that described for immunoglobulins. Recombination DJ relates to initially the chain beta. This process can concern or the junction of the D_β1 segment and one of the six J_β1 segments or the junction of the D_β2 segment with one of the six J_β2 segments. As described above, recombination DJ is supplemented by a V_β-to-D_βJ_β rearrangement. All the genes located in the intervals of the V_β-D_β-J_β complex are eliminated and the transcribed primary education synthesized comprises the constant segment (V_β-D_β-J_β-C_β). The post-transcriptionnelles modifications eliminate the Intron S and the translation of ARNm produces protein TCR _β.

The recombination of the chain alpha is done after the chain beta. It is similar to the rearrangement of the light chains of immunoglobulins (VJ). Assembly of a chain β and α form the TCR αβ which is present on the surface of a majority of lymphocytes T.

Note:

There exist two great types of TCR: αβ and γδ. Although the functions of the lymphocytes carrying these two types of different TCR, the gene loci coding the proteins γ and δ are recombined same manner.

Mechanism

Sequences signal of recombination

The loci of the genes V, D, J are flanked by Recombination Signal Sequences (RSSs) which are recognized by a group of enzyme known collectively like VDJ recombinases. RSS are constitute by a preserved heptamère palindromic, followed by an intercalating sequence of 12 or 23 nucleotides, then a preserved nonamère. Sequences RSS located into 3' (downstream) of the segment V and in 5' (upstream) of the segment J are recognized by the recombinase. Only associations of dissimilar RSS are effectively recombined, i.e. a RSS with an intercalating sequence of 12 nucleotides will be recombines with a RSS having one intercalating of 23 nucleotides. This is known like law 12/23.

VDJ recombinase

Recombinases VDJ are a collection of enzymes of which some are specific lymphocytes, and others are expressed in many cellular types. The first stages of recombination VDJ are dealt with by enzymes specific of the lymphocytes, called Recombination activating embarrassment -1 and -2 (RAG1 and RAG2). These enzymes join between them to recognize sequences RSS and to induce the cleavage of the DNA to sites RSS. This cut relates to one bit of DNA, which leads the formation of a hairpin.

Other enzymes VDJ recombinase are expressed in multiple cellular types and are implied in the repair of the DNA following the action of the RAG1 and RAG2.

References

Leland H Hartwell, Leroy Hood, Michael L. Goldberg, Ann E. Reynolds, Lee Mr. Silver, Ruth C. Veres (Genetics: From Genoa to Genomes, copyright 2000). Chapter 24, Evolution At the molecular level; pages 805-807 ISBN 0-07-540923-2
Janeway CA, Jr. et al. , Immunobiology. sixth ED. Garland Science, 2005 ISBN 0443073104}}
Abbas AK and Lichtman AH Cellular and Molecular Immunology. fifth ED. Saunders, Philadelphia, 2003 ISBN 0-7216-0008-5}}

Random links: