Affinity maturation
Affinity maturation is a biological process that occurs in the immune system, specifically in B cells. It is a mechanism that increases the antibody's binding affinity for its specific antigen during the immune response. This process is crucial for the adaptive immune system's ability to effectively combat infections and provide long-term immunity.
Overview
Affinity maturation occurs in the germinal center of lymph nodes after activation of B cells by an antigen. The activated B cells undergo rapid cell division and mutation of the genes that encode for the antibody's variable region. This process, known as somatic hypermutation, results in a pool of B cells that produce antibodies with slightly different antigen affinities.
Process
The process of affinity maturation involves several steps:
- Somatic hypermutation (SHM): This is the initial step in affinity maturation. It introduces point mutations at a high rate into the variable region of the antibody gene in B cells. The enzyme activation-induced cytidine deaminase (AID) is crucial for this process.
- Clonal selection: B cells with higher affinity antibodies have a survival advantage and are preferentially selected for proliferation. This process is facilitated by T follicular helper cells (Tfh).
- Class switch recombination (CSR): This is an optional step that changes the antibody's isotype to better suit the immune response's needs. Like SHM, CSR is also mediated by AID.
Role in Immunity
Affinity maturation plays a crucial role in the adaptive immune response. It allows the immune system to produce high-affinity antibodies that can effectively neutralize pathogens. Moreover, the process contributes to the formation of memory B cells, which provide long-term immunity against the same antigen.
Clinical Significance
Understanding the process of affinity maturation is essential in various clinical contexts, such as vaccine development and autoimmune diseases. For instance, vaccines aim to stimulate a strong immune response, including affinity maturation, to provide long-term protection against specific pathogens. On the other hand, dysregulation of affinity maturation can lead to the production of autoantibodies, contributing to the development of autoimmune diseases.
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Contributors: Prab R. Tumpati, MD