Osmosis from Elsevier - Somatic hypermutation and affinity maturation
The adaptive immune response is characterized by its specificity, achieved through the unique receptors on B and T cells, known as B cell receptors (BCR) and T cell receptors (TCR). These receptors undergo VDJ rearrangement to create a diverse set of receptors. B cells further enhance this diversity through somatic hypermutation, leading to affinity maturation, where B cells develop stronger responses to antigens. Activation of B cells occurs when antigens bind to BCRs, triggering a cascade of events including antigen presentation and interaction with helper T cells. This interaction leads to class switching and somatic hypermutation, facilitated by the enzyme activation-induced cytidine deaminase (AID). AID's role is crucial in both class switching and introducing mutations that enhance antigen affinity. Somatic hypermutation occurs in germinal centers and involves DNA repair mechanisms that introduce mutations, potentially increasing the affinity of BCRs for antigens. This process is akin to natural selection, where B cells with higher affinity survive as antigen levels decrease, leading to affinity maturation.
Key Points:
- Adaptive immune response is specific due to unique antigen receptors on B and T cells.
- VDJ rearrangement and somatic hypermutation increase receptor diversity and antigen affinity.
- B cell activation involves antigen binding, T cell interaction, and class switching.
- AID enzyme is crucial for class switching and somatic hypermutation in B cells.
- Affinity maturation ensures survival of B cells with high antigen affinity as antigen levels decrease.
Details:
1. 🔬 Adaptive Immune Response: B and T Cells
- The adaptive immune response is highly specific due to receptors on lymphocytes that identify unique pathogen antigens.
- Lymphocytes, specifically B and T cells, are key to this response, with B cells using B cell receptors (BCR) and T cells using T cell receptors (TCR).
- VDJ rearrangement in B and T cells generates diverse antigen receptors, enhancing immune specificity.
- B cells undergo somatic hypermutation to improve BCR diversity and antigen response through affinity maturation.
- BCRs are antibodies on B cell surfaces with variable regions for antigen binding and constant regions determining antibody class (e.g., IgM, IgG, IgD).
- T cells are crucial for identifying and destroying infected host cells, while B cells are primarily responsible for producing antibodies against antigens.
2. 🧬 B Cell Activation and Antibody Production
2.1. Initial B Cell Activation and Antigen Presentation
2.2. Class Switching and Antibody Production
3. ⚙️ Somatic Hypermutation and Affinity Maturation
3.1. Somatic Hypermutation Mechanism
3.2. DNA Repair Mechanisms
3.3. Impact on B Cell Antigen Specificity
3.4. Affinity Maturation and Immune Response
4. 🔁 Recap and Key Points on B Cell Affinity Maturation
- Somatic hypermutation occurs exclusively in B cells expressing the enzyme AID.
- AID introduces small mutations directly in the antigen binding site of the BCR in daughter cells.
- These changes in the variable region alter the affinity or strength of the BCR for its antigen.
- As antigen availability decreases, B cells with the lowest affinity die off, ensuring only those with the strongest affinity survive.
- This process is known as affinity maturation.