immunoglobulin heavy chain V-D-J recombination

Definition

Target type: biologicalprocess

The process in which immunoglobulin heavy chain V, D, and J gene segments are recombined within a single locus utilizing the conserved heptamer and nonomer recombination signal sequences (RSS). [GOC:add, ISBN:0781735149]

Immunoglobulin heavy chain V-D-J recombination is a complex process that generates a diverse repertoire of antibodies. It occurs in developing B lymphocytes and involves the rearrangement of three gene segments: V (variable), D (diversity), and J (joining). This rearrangement is essential for creating the unique antigen-binding sites of antibodies.

The process begins with the transcription of the immunoglobulin heavy chain locus, which contains multiple copies of V, D, and J gene segments. These segments are flanked by recombination signal sequences (RSS), which are conserved DNA motifs that guide the recombination process.

**1. RAG Recombinase Activity:**

* The recombination process is initiated by the RAG1 and RAG2 enzymes (Recombination Activating Genes).
* These enzymes recognize and bind to the RSSs flanking the V, D, and J segments.
* RAG1 cleaves the DNA at the RSS, creating a hairpin loop structure at the end of the DNA segment.

**2. VDJ Joining:**

* The cleaved DNA segments are then processed by a series of enzymes, including DNA-PKcs, Artemis, and Ku70/Ku80.
* These enzymes open the hairpin loops and process the DNA ends to create a single-stranded overhang.
* The overhangs are then joined together by the enzyme DNA ligase IV, forming a V-D-J rearrangement.

**3. Diversity Generation:**

* During the process of V-D-J recombination, several mechanisms contribute to antibody diversity:

* **Multiple Gene Segments:** The heavy chain locus contains hundreds of V, D, and J gene segments, allowing for a large number of possible combinations.
* **N-Nucleotide Addition:** Terminal deoxynucleotidyl transferase (TdT) randomly adds nucleotides to the ends of the rearranged segments.
* **P-Nucleotide Addition:** The RAG enzymes can add nucleotides to the DNA ends during the hairpin opening process.

**4. Allelic Exclusion:**

* Once a successful V-D-J recombination event occurs on one chromosome, the other chromosome is usually silenced. This ensures that each B cell expresses only one type of immunoglobulin heavy chain, a phenomenon known as allelic exclusion.

**5. Class Switch Recombination:**

* After V-D-J recombination, B cells can undergo class switch recombination, which alters the constant region of the antibody, allowing the cell to produce different antibody isotypes (e.g., IgM, IgG, IgA).

**Overall, V-D-J recombination is a highly regulated and intricate process that ensures the generation of a vast repertoire of antibodies, allowing the immune system to recognize and neutralize a wide range of pathogens.'
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Proteins (1)

Compounds (22)