Somatic recombination

Somatic recombination refers to the process in the immune system where DNA sequences are rearranged to form new combinations. This mechanism is crucial for the diversity of the antibody repertoire in B cells and the T cell receptor diversity in T cells. Somatic recombination allows the immune system to adapt and respond to a vast array of pathogens.

Overview

Somatic recombination occurs in the lymphocytes (B cells and T cells) of the immune system. It involves the cutting and joining of V (variable), D (diversity), and J (joining) gene segments for immunoglobulin (in B cells) and T cell receptor genes (in T cells). This process is mediated by the RAG1 and RAG2 proteins, which introduce double-strand breaks at specific DNA sequences. The DNA repair mechanisms of the cell then join these segments together, creating a unique V(D)J recombination that codes for a specific antigen receptor.

Mechanism

The process of somatic recombination can be broken down into several steps: 1. Recognition of recombination signal sequences (RSS) adjacent to V, D, and J segments by the RAG1 and RAG2 proteins. 2. Introduction of double-strand breaks between the RSS and the coding segments by the RAG complex. 3. Processing of the broken DNA ends to prepare them for joining. 4. Joining of the V, D, and J segments by the non-homologous end joining (NHEJ) pathway of DNA repair.

This process is tightly regulated to ensure that each B or T cell produces a unique receptor specificity.

Significance

Somatic recombination is essential for the adaptive immune response. The diversity generated by this process allows the immune system to recognize and respond to a wide variety of antigens. Without somatic recombination, the repertoire of antibodies and T cell receptors would be severely limited, compromising the ability of the immune system to fight infections.

Clinical Relevance

Abnormalities in the somatic recombination process can lead to immunodeficiencies, where the immune system is unable to respond effectively to pathogens. Additionally, errors in recombination can result in the production of self-reactive B or T cells, contributing to the development of autoimmune diseases.